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Name of journal: World Journal of GastroenterologyESPS Manuscript NO: 5748Columns: TOPIC HIGHLIGHTWJG 20th Anniversary Special Issues (9): Hepatitis B virusOutcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantationCongly SE et al. Viral hepatitis HIV co-infection liver transplantationStephen E Congly, Karen E Doucette, Carla S CoffinStephen E Congly, Carla S Coffin, Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB T2N 4Z6, CanadaKaren E Doucette, Division of Infectious Diseases, University of Alberta, Edmonton, AB T6G 2R3, CanadaAuthor contributions: Congly SE, Doucette KE and Coffin CS solely contributed to this paper.Correspondence to: Carla S Coffin, MD, MSc, FRCPC, Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, 6D21, Teaching, Research and Wellness Building 3280, Hospital Drive, Calgary, AB T2N 4Z6, Canada. cscoffin@ucalgary.caTelephone: +1-403-5925049 Fax: +1-403-5925090Received: September 24, 2013 Revised: October 22, 2013 Accepted: November 3, 2013Published online: AbstractLiver transplantation for human immunodeficiency virus (HIV) positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers. Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients co-infected with hepatitis B virus (HBV). However, liver transplantation in HIV positive patients with hepatitis C virus (HCV) has poorer outcomes overall, requiring careful selection of candidates. This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management. In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.Key words: Hepatitis B virus; Human immunodeficiency virus co-infection; Hepatitis C virus; Co-infection; Liver transplantationCore tip: Liver transplantation is not contraindicated in viral hepatitis patients co-infected with human immunodeficiency virus. Patients should meet standard listing criteria for liver transplantation. Management of these patients should be done through a multidisciplinary management approach including pharmacists and infectious diseases physicians. Congly SE, Doucette KE, Coffin CS. Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation. World J Gastroenterol 2013; Available from: URL: DOI: transplantation offers the promise of improved quantity and quality of life for patients with end stage liver disease with 1-year survival approaching 90% ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"fnvjug247","properties":{"formattedCitation":"{\\rtf \\super [1]\\nosupersub{}}","plainCitation":"[1]"},"citationItems":[{"id":11,"uris":[""],"uri":[""],"itemData":{"id":11,"type":"article-journal","title":"OPTN/SRTR 2011 Annual Data Report: liver","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"73-102","volume":"13 Suppl 1","source":"NCBI PubMed","abstract":"The current liver allocation system, introduced in 2002, decreased the importance of waiting time for allocation priorities; the number of active wait-listed candidates and median waiting times were immediately reduced. However, the total number of adult wait-listed candidates has increased since 2002, and median waiting time has increased since 2006. Pretransplant mortality rates have been stable, but the number of candidates withdrawn from the list as being too sick to undergo transplant nearly doubled between 2009 and 2011. Deceased donation rates have remained stable, with an increasing proportion of expanded criteria donors. Living donation has decreased over the past 10 years. Transplant outcomes remain robust, with continuously improving graft survival rates for deceased donor, living donor, and donation after circulatory death livers. Numbers of new and prevalent pediatric candidates on the waiting list have decreased. Pediatric pretransplant mortality has decreased, most dramatically for candidates aged less than 1 year. The transplant rate has increased since 2002, and is highest in candidates aged less than 1 year. Graft survival continues to improve for pediatric recipients of deceased donor and living donor livers. Incidence of acute rejections increases with time after transplant. Posttransplant lymphoproliferative disorder remains an important concern in pediatric recipients.","DOI":"10.1111/ajt.12021","ISSN":"1600-6143","note":"PMID: 23237697","shortTitle":"OPTN/SRTR 2011 Annual Data Report","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Kim","given":"W R"},{"family":"Stock","given":"P G"},{"family":"Smith","given":"J M"},{"family":"Heimbach","given":"J K"},{"family":"Skeans","given":"M A"},{"family":"Edwards","given":"E B"},{"family":"Harper","given":"A M"},{"family":"Snyder","given":"J J"},{"family":"Israni","given":"A K"},{"family":"Kasiske","given":"B L"}],"issued":{"date-parts":[["2013",1]]},"PMID":"23237697"}}],"schema":""} [1]. Historically, HIV infection was considered to be a contraindication to transplantation ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2hp1j08r8p","properties":{"formattedCitation":"{\\rtf \\super [2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"716-726","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.","DOI":"10.1002/lt.23411","ISSN":"1527-6473","note":"PMID: 22328294","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Terrault","given":"Norah A"},{"family":"Roland","given":"Michelle E"},{"family":"Schiano","given":"Thomas"},{"family":"Dove","given":"Lorna"},{"family":"Wong","given":"Michael T"},{"family":"Poordad","given":"Fred"},{"family":"Ragni","given":"Margaret V"},{"family":"Barin","given":"Burc"},{"family":"Simon","given":"David"},{"family":"Olthoff","given":"Kim M"},{"family":"Johnson","given":"Lynt"},{"family":"Stosor","given":"Valentina"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Fung","given":"John"},{"family":"Sherman","given":"Kenneth E"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Slakey","given":"Douglas"},{"family":"Berg","given":"Carl L"},{"family":"Carlson","given":"Laurie"},{"family":"Ferrell","given":"Linda"},{"family":"Stablein","given":"Donald M"},{"family":"Odim","given":"Jonah"},{"family":"Fox","given":"Lawrence"},{"family":"Stock","given":"Peter G"},{"family":"Solid Organ Transplantation in HIV: Multi-Site Study Investigators","given":""}],"issued":{"date-parts":[["2012",6]]},"PMID":"22328294"}}],"schema":""} [2] with early outcomes in the pre-highly active anti-retroviral (HAART) era being abysmal ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2i8sr7uru2","properties":{"formattedCitation":"{\\rtf \\super [3]\\nosupersub{}}","plainCitation":"[3]"},"citationItems":[{"id":187,"uris":[""],"uri":[""],"itemData":{"id":187,"type":"article-journal","title":"Outcome of orthotopic liver transplantation in patients with haemophilia","container-title":"Gut","page":"744-749","volume":"42","issue":"5","source":"NCBI PubMed","abstract":"BACKGROUND: Many patients with haemophilia have developed cirrhosis or hepatocellular carcinoma due to transfusion acquired chronic viral hepatitis.\nAIMS: To assess the long term outcome of all haemophilic patients reported to have undergone orthotopic liver transplantation.\nMETHODS: Transplant centres of patients identified by medical database search were contacted and survival data assessed by Kaplan-Meier analysis.\nRESULTS: Twenty six haemophilic men (median age 46 years, range 5-63 years) underwent orthotopic liver transplantation in 16 centres between 1982 and 1996. Indications for transplantation were hepatitis C cirrhosis (69%), hepatitis B with or without C cirrhosis (15%), viral hepatitis related hepatocellular carcinoma (12%), and biliary atresia (4%). Six patients (23%) were infected with human immunodeficiency virus (HIV). Postoperatively, the median time to normal clotting factor levels was 24 hours (range 0-48 hours) and exogenous clotting factors were stopped at a median of 24 hours (range 0-480 hours). Four patients (15%) had bleeding complications. The one and three year survival of HIV positive recipients (67% and 23%) was significantly poorer (p = 0.0003) than that of HIV negative recipients (90% and 83%). Coagulopathy was cured in all patients surviving more than 12 days post-transplant. Six of the 20 patients (30%) with hepatitis C cirrhosis pretransplant had evidence of disease recurrence at a mean of nine months post-transplant.\nCONCLUSIONS: Hepatitis C cirrhosis is the most common indication for orthotopic liver transplantation in patients with haemophilia. Transplantation results in long term cure of haemophilia but may be complicated by the effects of HIV infection or recurrent viral hepatitis.","ISSN":"0017-5749","note":"PMID: 9659174","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Gordon","given":"F H"},{"family":"Mistry","given":"P K"},{"family":"Sabin","given":"C A"},{"family":"Lee","given":"C A"}],"issued":{"date-parts":[["1998",5]]},"PMID":"9659174"}}],"schema":""} [3]. With the improvement of HAART, patients with HIV have comparable life expectancy to the general population ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"26f51ebe6k","properties":{"formattedCitation":"{\\rtf \\super [4,5]\\nosupersub{}}","plainCitation":"[4,5]"},"citationItems":[{"id":525,"uris":[""],"uri":[""],"itemData":{"id":525,"type":"article-journal","title":"Survival of persons with and without HIV infection in Denmark, 1995-2005","container-title":"Annals of internal medicine","page":"87-95","volume":"146","issue":"2","source":"NCBI PubMed","abstract":"BACKGROUND: The expected survival of HIV-infected patients is of major public health interest.\nOBJECTIVE: To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population.\nDESIGN: Population-based cohort study.\nSETTING: All HIV-infected persons receiving care in Denmark from 1995 to 2005.\nPATIENTS: Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex, date of birth, and municipality of residence.\nMEASUREMENTS: The authors computed Kaplan-Meier life tables with age as the time scale to estimate survival from age 25 years. Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient's HIV diagnosis until death, emigration, or 1 May 2005.\nRESULTS: 3990 HIV-infected patients and 379,872 persons from the general population were included in the study, yielding 22,744 (median, 5.8 y/person) and 2,689,287 (median, 8.4 years/person) person-years of observation. Three percent of participants were lost to follow-up. From age 25 years, the median survival was 19.9 years (95% CI, 18.5 to 21.3) among patients with HIV infection and 51.1 years (CI, 50.9 to 51.5) among the general population. For HIV-infected patients, survival increased to 32.5 years (CI, 29.4 to 34.7) during the 2000 to 2005 period. In the subgroup that excluded persons with known hepatitis C coinfection (16%), median survival was 38.9 years (CI, 35.4 to 40.1) during this same period. The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age, whereas the excess mortality rate increased with increasing age.\nLIMITATIONS: The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years.\nCONCLUSIONS: The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era. However, an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population.","ISSN":"1539-3704","note":"PMID: 17227932","journalAbbreviation":"Ann. Intern. Med.","language":"eng","author":[{"family":"Lohse","given":"Nicolai"},{"family":"Hansen","given":"Ann-Brit Eg"},{"family":"Pedersen","given":"Gitte"},{"family":"Kronborg","given":"Gitte"},{"family":"Gerstoft","given":"Jan"},{"family":"S?rensen","given":"Henrik Toft"},{"family":"Vaeth","given":"Michael"},{"family":"Obel","given":"Niels"}],"issued":{"date-parts":[["2007",1,16]]},"PMID":"17227932"}},{"id":527,"uris":[""],"uri":[""],"itemData":{"id":527,"type":"article-journal","title":"Life expectancy living with HIV: recent estimates and future implications","container-title":"Current opinion in infectious diseases","page":"17-25","volume":"26","issue":"1","source":"NCBI PubMed","abstract":"PURPOSE OF REVIEW: The life expectancy of people living with HIV has dramatically increased since effective antiretroviral therapy has been available, and still continues to improve. Here, we review the latest literature on estimates of life expectancy and consider the implications for future research.\nRECENT FINDINGS: With timely diagnosis, access to a variety of current drugs and good lifelong adherence, people with recently acquired infections can expect to have a life expectancy which is nearly the same as that of HIV-negative individuals. Modelling studies suggest that life expectancy could improve further if there were increased uptake of HIV testing, better antiretroviral regimens and treatment strategies, and the adoption of healthier lifestyles by those living with HIV. In particular, earlier diagnosis is one of the most important factors associated with better life expectancy. A consequence of improved survival is the increasing number of people with HIV who are aged over 50 years old, and further research into the impact of ageing on HIV-positive people will therefore become crucial. The development of age-specific HIV treatment and management guidelines is now called for.\nSUMMARY: Analyses on cohort studies and mathematical modelling studies have been used to estimate life expectancy of those with HIV, providing useful insights of importance to individuals and healthcare planning.","DOI":"10.1097/QCO.0b013e32835ba6b1","ISSN":"1473-6527","note":"PMID: 23221765","shortTitle":"Life expectancy living with HIV","journalAbbreviation":"Curr. Opin. Infect. Dis.","language":"eng","author":[{"family":"Nakagawa","given":"Fumiyo"},{"family":"May","given":"Margaret"},{"family":"Phillips","given":"Andrew"}],"issued":{"date-parts":[["2013",2]]},"PMID":"23221765"}}],"schema":""} [4,5]; similar to those with other chronic medical conditions, such as diabetes. As such, liver transplant is now considered a potential treatment option to the over 1.1 million infected with HIV in the United States ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"rf514kjn9","properties":{"formattedCitation":"{\\rtf \\super [6]\\nosupersub{}}","plainCitation":"[6]"},"citationItems":[{"id":343,"uris":[""],"uri":[""],"itemData":{"id":343,"type":"report","title":"Monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 U.S. dependent areas—2010. HIV Surveillance Supplemental Report 2013;18(No. 2, part B)","URL":" surveillance/resources/reports/#supplemental","author":[{"family":"Centers for Disease Control and Prevention","given":""}],"issued":{"date-parts":[["2013",1]]}}}],"schema":""} [6] and 34 million worldwide ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2okegntjf","properties":{"formattedCitation":"{\\rtf \\super [7]\\nosupersub{}}","plainCitation":"[7]"},"citationItems":[{"id":344,"uris":[""],"uri":[""],"itemData":{"id":344,"type":"book","title":"Global Report: UNAIDS Report on the Global AIDS epidemic: 2012","publisher":"UNAIDS","publisher-place":"[Geneva]","source":"Open WorldCat","event-place":"[Geneva]","abstract":"The 2012 edition of the UNAIDS Report is based on the latest data from 186 countries who have submitted comprehensive reports on progress in their national AIDS response with 96% of the 193 United Nations Member States reporting the highest response rates of any international health and development monitoring mechanism -- a vivid reflection of the breadth and depth of global commitment to the response to AIDS.","URL":"","ISBN":"9789291739967 9291739960","shortTitle":"Global Report","language":"English","author":[{"family":"Joint United Nations Programme on HIV/AIDS","given":""},{"family":"United Nations","given":""}],"issued":{"date-parts":[["2012"]]},"accessed":{"date-parts":[["2013",9,3]]}}}],"schema":""} [7].Patients living with HIV have a significant burden of liver disease; one large series suggests that liver disease is related to over 14% of all cause mortality ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2f5bq45ji2","properties":{"formattedCitation":"{\\rtf \\super [8]\\nosupersub{}}","plainCitation":"[8]"},"citationItems":[{"id":250,"uris":[""],"uri":[""],"itemData":{"id":250,"type":"article-journal","title":"Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study","container-title":"Archives of internal medicine","page":"1632-1641","volume":"166","issue":"15","source":"NCBI PubMed","abstract":"BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases.\nMETHODS: We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death.\nRESULTS: There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for <50 vs > or =500/microL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02).\nCONCLUSIONS: Liver-related death was the most frequent cause of non-AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.","DOI":"10.1001/archinte.166.15.1632","ISSN":"0003-9926","note":"PMID: 16908797","shortTitle":"Liver-related deaths in persons infected with the human immunodeficiency virus","journalAbbreviation":"Arch. Intern. Med.","language":"eng","author":[{"family":"Weber","given":"Rainer"},{"family":"Sabin","given":"Caroline A"},{"family":"Friis-M?ller","given":"Nina"},{"family":"Reiss","given":"Peter"},{"family":"El-Sadr","given":"Wafaa M"},{"family":"Kirk","given":"Ole"},{"family":"Dabis","given":"Francois"},{"family":"Law","given":"Matthew G"},{"family":"Pradier","given":"Christian"},{"family":"De Wit","given":"Stephane"},{"family":"Akerlund","given":"B?rje"},{"family":"Calvo","given":"Gonzalo"},{"family":"Monforte","given":"Antonella d'Arminio"},{"family":"Rickenbach","given":"Martin"},{"family":"Ledergerber","given":"Bruno"},{"family":"Phillips","given":"Andrew N"},{"family":"Lundgren","given":"Jens D"}],"issued":{"date-parts":[["2006",8,14]]},"PMID":"16908797"}}],"schema":""} [8] with three-quarters of this being attributable to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The increased burden of co-infection with HBV or HCV in HIV patients relates to similar mechanisms of transmission of the viruses such as sexual or vertical transmission, blood transfusion or intravenous (iv) drug use. In areas of low HBV endemicity, such as North America and Western Europe, HIV and HBV co-infections occur primarily in immigrant populations and in adult populations due to shared sexual and percutaneous modes of transmission ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"u67gvvfeg","properties":{"formattedCitation":"{\\rtf \\super [9]\\nosupersub{}}","plainCitation":"[9]"},"citationItems":[{"id":345,"uris":[""],"uri":[""],"itemData":{"id":345,"type":"article-journal","title":"The epidemiology, natural history and prevention of hepatitis B: implications of HIV coinfection","container-title":"Antiviral therapy","page":"H3-13","volume":"12 Suppl 3","source":"NCBI PubMed","abstract":"Approximately 350 million people have chronic hepatitis B infection, a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Patients who are infected through parenteral or sexual transmission are also at risk for acquisition of HIV. Concomitant HIV infection can lead to an increased risk of morbidity and mortality from hepatitis B virus (HBV)-related cirrhosis, end-stage liver disease and HCC. This review will focus on the epidemiology, natural history and prevention of HBV infection and the modulating effect of HIV on the clinical expression of HBV disease.","ISSN":"2040-2058","note":"PMID: 18284178","shortTitle":"The epidemiology, natural history and prevention of hepatitis B","journalAbbreviation":"Antivir. Ther. (Lond.)","language":"eng","author":[{"family":"McGovern","given":"Barbara H"}],"issued":{"date-parts":[["2007"]]},"PMID":"18284178"}}],"schema":""} [9]. The prevalence of HBV co-infection in Western countries has been reported as between 6%-14% ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"f2uk5k80s","properties":{"formattedCitation":"{\\rtf \\super [10]\\nosupersub{}}","plainCitation":"[10]"},"citationItems":[{"id":410,"uris":[""],"uri":[""],"itemData":{"id":410,"type":"article-journal","title":"Epidemiology of viral hepatitis and HIV co-infection","container-title":"Journal of hepatology","page":"S6-9","volume":"44","issue":"1 Suppl","source":"NCBI PubMed","abstract":"Worldwide, hepatitis B virus (HBV) accounts for an estimated 370 million chronic infections, hepatitis C virus (HCV) for an estimated 130 million, and HIV for an estimated 40 million. In HIV-infected persons, an estimated 2-4 million have chronic HBV co-infection and 4-5 million have HCV co-infection. HBV, HCV and HIV share common routes of transmission, but they differ in their prevalence by geographic region and the efficiency by which certain types of exposures transmit them. Among HIV-positive persons studied from Western Europe and the USA, chronic HBV infection has been found in 6-14% overall, including 4-6% of heterosexuals, 9-17% of men who have sex with men (MSM), and 7-10% of injection drug users. HCV infection has been found in 25-30% of HIV-positive persons overall; 72-95% of injection drug users, 1-12% of MSM and 9-27% of heterosexuals. The characteristics of HIV infected persons differ according to the co-infecting hepatitis virus, their epidemiologic patterns may change over time, and surveillance systems are needed to monitor their infection patterns in order to ensure that prevention measures are targeted appropriately.","DOI":"10.1016/j.jhep.2005.11.004","ISSN":"0168-8278","note":"PMID: 16352363","journalAbbreviation":"J. Hepatol.","language":"eng","author":[{"family":"Alter","given":"Miriam J"}],"issued":{"date-parts":[["2006"]]},"PMID":"16352363"}}],"schema":""} [10] with rates of co-infection in endemic areas such as Africa and southeast Asia nearing 30% ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"21u1cd98c0","properties":{"formattedCitation":"{\\rtf \\super [11]\\nosupersub{}}","plainCitation":"[11]"},"citationItems":[{"id":412,"uris":[""],"uri":[""],"itemData":{"id":412,"type":"article-journal","title":"Viral hepatitis in HIV infection","container-title":"The New England journal of medicine","page":"1445-1454","volume":"356","issue":"14","source":"NCBI PubMed","DOI":"10.1056/NEJMra065142","ISSN":"1533-4406","note":"PMID: 17409326","journalAbbreviation":"N. Engl. J. Med.","language":"eng","author":[{"family":"Koziel","given":"Margaret James"},{"family":"Peters","given":"Marion G"}],"issued":{"date-parts":[["2007",4,5]]},"PMID":"17409326"}}],"schema":""} [11]. For HCV, the rates of co-infection also reflect the shared risk factors for transmission with approximately 10% acquired through high risk sexual exposures and the vast majority via blood-borne contact ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1vrh3j0l4h","properties":{"formattedCitation":"{\\rtf \\super [12]\\nosupersub{}}","plainCitation":"[12]"},"citationItems":[{"id":287,"uris":[""],"uri":[""],"itemData":{"id":287,"type":"article-journal","title":"Liver transplantation in HIV-positive patients","container-title":"Clinical transplantation","page":"68-74","volume":"23 Suppl 21","source":"NCBI PubMed","abstract":"Death from end-stage liver disease (ESLD) because of chronic hepatitis B and C has become an increasing problem in human immunodeficiency virus (HIV)-infected patients in the last years. This is mainly because of the dramatic decrease of HIV-related morbidity and mortality since the introduction of highly active antiretroviral therapy (HAART). Although the data on the outcome of liver transplantation in HIV-infected recipients with ESLD is limited, overall results seem comparable to non-HIV-infected recipients. Therefore, liver transplant centres around the world are increasingly accepting HIV-infected individuals as organ recipients. Post-transplantation control of HIV replication is achieved by continuing HAART. As in non-HIV-infected patients, hepatitis B virus recurrence is efficiently prevented by hepatitis B immunoglobulin and antiviral therapy. Re-infection of the allograft with hepatitis C virus, however, remains an important problem, and progress to allograft cirrhosis may even be more rapid than in HIV-negative patients. Interactions in drug metabolism between the HAART components and the immunosuppressive drugs are difficult to predict and require close monitoring of drug levels and dose adjustments. The complexity in this setting makes close cooperation between transplant surgeons, hepatologists, HIV-clinicians and pharmacologists mandatory. As experience on liver transplantation in HIV-infected individuals is still limited, to date results from large prospective trials addressing key issues are needed.","DOI":"10.1111/j.1399-0012.2009.01112.x","ISSN":"1399-0012","note":"PMID: 19930319","journalAbbreviation":"Clin Transplant","language":"eng","author":[{"family":"Eisenbach","given":"Christoph"},{"family":"Merle","given":"Uta"},{"family":"Stremmel","given":"Wolfgang"},{"family":"Encke","given":"Jens"}],"issued":{"date-parts":[["2009",12]]},"PMID":"19930319"}}],"schema":""} [12]. The global burden of HIV co-infection is significant with approximately 7 million persons co-infected with HCV and 4 million with HBV worldwide ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"7nicmic5u","properties":{"formattedCitation":"{\\rtf \\super [13,14]\\nosupersub{}}","plainCitation":"[13,14]"},"citationItems":[{"id":291,"uris":[""],"uri":[""],"itemData":{"id":291,"type":"article-journal","title":"Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel","container-title":"AIDS (London, England)","page":"1399-1410","volume":"22","issue":"12","source":"NCBI PubMed","abstract":"Nearly 10% of the estimated 36 million people having HIV worldwide suffer from chronic hepatitis B virus (HBV) infection. The advent of new antiviral agents against HBV and the recent availability of improved molecular diagnostic tools have revolutioned the management of HIV/HBV coinfected patients. The present study represents an update of the current knowledge about HBV/HIV coinfection and an intent to provide practical advise about how to give the best care to HIV-infected persons with chronic hepatitis B.","DOI":"10.1097/QAD.0b013e3282f8b46f","ISSN":"1473-5571","note":"PMID: 18614862","shortTitle":"Care of HIV patients with chronic hepatitis B","journalAbbreviation":"AIDS","language":"eng","author":[{"family":"Soriano","given":"Vincent"},{"family":"Puoti","given":"Massimo"},{"family":"Peters","given":"Marion"},{"family":"Benhamou","given":"Yves"},{"family":"Sulkowski","given":"Mark"},{"family":"Zoulim","given":"Fabien"},{"family":"Mauss","given":"Stefan"},{"family":"Rockstroh","given":"Juergen"}],"issued":{"date-parts":[["2008",7,31]]},"PMID":"18614862"}},{"id":289,"uris":[""],"uri":[""],"itemData":{"id":289,"type":"article-journal","title":"Viral hepatitis and HIV co-infection","container-title":"Antiviral research","page":"303-315","volume":"85","issue":"1","source":"NCBI PubMed","abstract":"Chronic hepatitis B virus (HBV) infection is overall recognised in 10% of HIV+ persons worldwide, with large differences according to geographical region. Chronic hepatitis C virus (HCV) infection affects 25% of HIV+ individuals, with greater rates ( approximately 75%) in intravenous drug users and persons infected through contaminated blood or blood products. HIV-hepatitis co-infected individuals show an accelerated course of liver disease, with faster progression to cirrhosis. The number of anti-HBV drugs has increased in the last few years, and some agents (e.g. lamivudine, emtricitabine, tenofovir) also exert significant activity against HIV. Emergence of drug resistance challenges the long-term benefit of anti-HBV monotherapy, mainly with lamivudine. The results using new more potent anti-HBV drugs (e.g. tenofovir) are very promising, with prospects for stopping or even revert HBV-related liver damage in most cases. With respect to chronic hepatitis C, the combination of pegylated interferon plus ribavirin given for 1 year permits to achieve sustained HCV clearance in no more than 40% of HIV-HCV co-infected patients. Thus, new direct anti-HCV drugs are eagerly awaited for this population. Although being a minority, HIV+ patients with delta hepatitis and those with multiple hepatitis show the worst prognosis. Appropriate diagnosis and monitoring of chronic viral hepatitis, including the use of non-invasive tools for assessing liver fibrosis and measurement of viral load, may allow to confront adequately chronic viral hepatitis in HIV+ patients, preventing the development of end-stage liver disease, for which the only option available is liver transplantation. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.","DOI":"10.1016/j.antiviral.2009.10.021","ISSN":"1872-9096","note":"PMID: 19887087","journalAbbreviation":"Antiviral Res.","language":"eng","author":[{"family":"Soriano","given":"Vincent"},{"family":"Vispo","given":"Eugenia"},{"family":"Labarga","given":"Pablo"},{"family":"Medrano","given":"Jose"},{"family":"Barreiro","given":"Pablo"}],"issued":{"date-parts":[["2010",1]]},"PMID":"19887087"}}],"schema":""} [13,14]. IMPACT OF VIRAL HEPATITIS/HIV CO-INFECTIONPatients co-infected with either HBV or HCV have more aggressive liver disease than those with mono-infection. In a large epidemiological study of 23441 patients infected with HIV, HIV-HBV co-infected patients were reported to have a 3-fold higher risk of liver related mortality compared to HBV mono-infection ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"XwDIW1Dv","properties":{"formattedCitation":"{\\rtf \\super [8]\\nosupersub{}}","plainCitation":"[8]"},"citationItems":[{"id":250,"uris":[""],"uri":[""],"itemData":{"id":250,"type":"article-journal","title":"Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study","container-title":"Archives of internal medicine","page":"1632-1641","volume":"166","issue":"15","source":"NCBI PubMed","abstract":"BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases.\nMETHODS: We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death.\nRESULTS: There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for <50 vs > or =500/microL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02).\nCONCLUSIONS: Liver-related death was the most frequent cause of non-AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.","DOI":"10.1001/archinte.166.15.1632","ISSN":"0003-9926","note":"PMID: 16908797","shortTitle":"Liver-related deaths in persons infected with the human immunodeficiency virus","journalAbbreviation":"Arch. Intern. Med.","language":"eng","author":[{"family":"Weber","given":"Rainer"},{"family":"Sabin","given":"Caroline A"},{"family":"Friis-M?ller","given":"Nina"},{"family":"Reiss","given":"Peter"},{"family":"El-Sadr","given":"Wafaa M"},{"family":"Kirk","given":"Ole"},{"family":"Dabis","given":"Francois"},{"family":"Law","given":"Matthew G"},{"family":"Pradier","given":"Christian"},{"family":"De Wit","given":"Stephane"},{"family":"Akerlund","given":"B?rje"},{"family":"Calvo","given":"Gonzalo"},{"family":"Monforte","given":"Antonella d'Arminio"},{"family":"Rickenbach","given":"Martin"},{"family":"Ledergerber","given":"Bruno"},{"family":"Phillips","given":"Andrew N"},{"family":"Lundgren","given":"Jens D"}],"issued":{"date-parts":[["2006",8,14]]},"PMID":"16908797"}}],"schema":""} [8]. Differences in survival were demonstrated in the early HAART era; a Taiwan study showed a 5-year survival of 75% in patients with HIV and chronic hepatitis B [positive serum hepatitis B surface antigen (HBsAg)] versus approximately 90% survival in HBsAg-negative, HIV infected patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"oh1mdib2j","properties":{"formattedCitation":"{\\rtf \\super [15]\\nosupersub{}}","plainCitation":"[15]"},"citationItems":[{"id":383,"uris":[""],"uri":[""],"itemData":{"id":383,"type":"article-journal","title":"Evolution of hepatitis B serological markers in HIV-infected patients receiving highly active antiretroviral therapy","container-title":"Clinical infectious diseases: an official publication of the Infectious Diseases Society of America","page":"1221-1229","volume":"45","issue":"9","source":"NCBI PubMed","abstract":"BACKGROUND: Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART).\nMETHODS: During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers.\nRESULTS: After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively.\nCONCLUSIONS: Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.","DOI":"10.1086/522173","ISSN":"1537-6591","note":"PMID: 17918088","journalAbbreviation":"Clin. Infect. Dis.","language":"eng","author":[{"family":"Sheng","given":"Wang-Huei"},{"family":"Kao","given":"Jia-Horng"},{"family":"Chen","given":"Pei-Jer"},{"family":"Huang","given":"Li-Ming"},{"family":"Chang","given":"Sui-Yuan"},{"family":"Sun","given":"Hsin-Yun"},{"family":"Hung","given":"Chien-Ching"},{"family":"Chen","given":"Mao-Yuan"},{"family":"Chang","given":"Shan-Chwen"}],"issued":{"date-parts":[["2007",11,1]]},"PMID":"17918088"}}],"schema":""} [15]. A subsequent meta-analysis of the co-infected population was concordant with this finding, although HAART did reduce the risk of death from 1.6 (95%CI: 1.07-2.39) to 1.28 (95%CI: 1.07-2.39) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1qq5lsj0if","properties":{"formattedCitation":"{\\rtf \\super [16]\\nosupersub{}}","plainCitation":"[16]"},"citationItems":[{"id":385,"uris":[""],"uri":[""],"itemData":{"id":385,"type":"article-journal","title":"Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis","container-title":"Clinical infectious diseases: an official publication of the Infectious Diseases Society of America","page":"1763-1771","volume":"48","issue":"12","source":"NCBI PubMed","abstract":"BACKGROUND: The effect of hepatitis B virus (HBV) infection on the natural history of human immunodeficiency virus (HIV) disease remains uncertain. Therefore, a retrospective cohort study was conducted to examine the influence of HIV-HBV coinfection on AIDS development and overall mortality. Moreover, our results were added to those of previous studies in a literature-based meta-analysis.\nMETHODS: Serum samples obtained from HIV-seropositive patients from 1984 through 2003 were retrospectively tested for hepatitis B surface antigen. Multivariable analyses were performed using Poisson and logistic regression models. For meta-analytic purposes, eligible articles were identified and relevant data were abstracted. Pooled estimates of effect were calculated applying fixed and random effects models.\nRESULTS: The prevalence of chronic HBV infection (documented hepatitis B surface antigen seropositivity for >6 months) among 1729 HIV-positive patients was approximately 6%. The multivariable analyses in our primary study revealed no significant impact of concomitant HIV-HBV infection on progression to AIDS and all-cause mortality. However, a meta-analysis performed on data from 12,382 patients enrolled in 11 studies revealed a significant effect of HIV-HBV coinfection on overall mortality (pooled effect estimate, 1.36; 95% confidence interval, 1.12-1.64). The increased rate of death among coinfected individuals was observed in the meta-analyses of studies conducted both before (pooled effect estimate, 1.60; 95% confidence interval, 1.07-2.39) and after (pooled effect estimate, 1.28; 95% confidence interval, 1.03-1.60) commencement of highly active antiretroviral therapy.\nCONCLUSIONS: HIV-HBV coinfection seems to affect all-cause mortality, and strategies to reduce liver damage in patients coinfected with HIV and HBV are justified.","DOI":"10.1086/599110","ISSN":"1537-6591","note":"PMID: 19435436","shortTitle":"Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals","journalAbbreviation":"Clin. Infect. Dis.","language":"eng","author":[{"family":"Nikolopoulos","given":"Georgios K"},{"family":"Paraskevis","given":"Dimitrios"},{"family":"Hatzitheodorou","given":"Eleni"},{"family":"Moschidis","given":"Zissis"},{"family":"Sypsa","given":"Vana"},{"family":"Zavitsanos","given":"Xenophon"},{"family":"Kalapothaki","given":"Victoria"},{"family":"Hatzakis","given":"Angelos"}],"issued":{"date-parts":[["2009",6,15]]},"PMID":"19435436"}}],"schema":""} [16]. Accordingly, HIV co-infected patients without HAART seem to have more aggressive HBV-related liver disease and progression to cirrhosis ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"19thjpr0t","properties":{"formattedCitation":"{\\rtf \\super [17]\\nosupersub{}}","plainCitation":"[17]"},"citationItems":[{"id":297,"uris":[""],"uri":[""],"itemData":{"id":297,"type":"article-journal","title":"Influence of HIV infection on the response to interferon therapy and the long-term outcome of chronic hepatitis B","container-title":"Gastroenterology","page":"1812-1822","volume":"123","issue":"6","source":"NCBI PubMed","abstract":"BACKGROUND & AIMS: The outcome of chronic hepatitis B and the efficacy of interferon alfa (IFN-alpha) remain controversial in human immunodeficiency virus (HIV)-positive patients. We analyzed the influence of HIV coinfection on the response to IFN-alpha therapy, long-term virologic status, progression to cirrhosis, and mortality.\nMETHODS: This was a retrospective follow-up cohort study of 141 consecutive hepatitis B e antigen-positive patients (69 HIV positive) followed up for 45 months.\nRESULTS: The short-term response to IFN-alpha therapy was not significantly different in HIV-positive and HIV-negative patients (28% vs. 51%; P = 0.06) but was poorer in cases of low CD4 cell count (P = 0.038). The hepatitis B virus (HBV) reactivation rate was higher in HIV-positive patients (P = 0.033) and was associated with low CD4 cell count. The risk of cirrhosis was higher in HIV-positive patients with a CD4 cell count <200/mm(3) (relative risk [RR], 4.57; P = 0.007), in IFN-alpha-untreated patients (RR, 2.63; P = 0.041), in patients older than 33 years (RR, 4.59; P = 0.008), and in cases of high necroinflammatory score at baseline (RR, 1.27; P = 0.010). Cirrhosis-related death was more frequent in HIV-positive patients with low CD4 cell count at baseline (P = 0.041), in alcohol consumers (P = 0.001), in IFN-alpha-untreated patients (P = 0.052), and in patients with high histology activity index at baseline (P = 0.005).\nCONCLUSIONS: HIV coinfection was associated with poorer response to IFN-alpha therapy, more frequent HBV reactivations, and increased incidence of cirrhosis and cirrhosis-related death in cases of low CD4 count. IFN-alpha therapy decreased the incidence of HBV cirrhosis regardless of HIV status or serologic response.","DOI":"10.1053/gast.2002.37061","ISSN":"0016-5085","note":"PMID: 12454838","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Di Martino","given":"Vincent"},{"family":"Thevenot","given":"Thierry"},{"family":"Colin","given":"Jean-Fran?ois"},{"family":"Boyer","given":"Nathalie"},{"family":"Martinot","given":"Michèle"},{"family":"Degos","given":"Fran?oise"},{"family":"Coulaud","given":"Jean-Pierre"},{"family":"Vilde","given":"Jean-Louis"},{"family":"Vachon","given":"Fran?ois"},{"family":"Degott","given":"Claude"},{"family":"Valla","given":"Dominique"},{"family":"Marcellin","given":"Patrick"}],"issued":{"date-parts":[["2002",12]]},"PMID":"12454838"}}],"schema":""} [17]. As well, HBV co-infection has also been demonstrated to adversely impact HIV patient outcomes either with or without HAART ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"uFSk4GVj","properties":{"formattedCitation":"{\\rtf \\super [18,19]\\nosupersub{}}","plainCitation":"[18,19]"},"citationItems":[{"id":299,"uris":[""],"uri":[""],"itemData":{"id":299,"type":"article-journal","title":"Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV seroconverters","container-title":"The Journal of infectious diseases","page":"185-193","volume":"205","issue":"2","source":"NCBI PubMed","abstract":"BACKGROUND: Understanding the impact of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV disease. We evaluated HBV coinfection and HIV-related disease progression in a cohort of HIV seroconverters.\nMETHODS: Participants with HIV diagnosis seroconversion window of ≤ 3 years and serologically confirmed HBV infection (HB) status were classified at baseline into 4 HB groups. The risk of clinical AIDS/death in HIV seroconverters was calculated by HB status.\nRESULTS: Of 2352 HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB. Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15-2.71); 3.27 (2.71-3.84); 3.75 (2.25-5.25); and 5.41 (3.41-7.42), respectively. The multivariable risk of clinical AIDS/death was significantly higher in the chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95% CI, 1.20-2.69); while the HRs were increased but nonsignificant for those with resolved HB (HR, 1.17; 95% CI, .94-1.46) and isolated HBcAb (HR, 1.14; 95% CI, .75-1.75).\nCONCLUSIONS: HBV coinfection has a significant impact on HIV outcomes. The hazard for an AIDS or death event is almost double for those with chronic HB compared, with HIV-monoinfected persons.","DOI":"10.1093/infdis/jir720","ISSN":"1537-6613","note":"PMID: 22147794","journalAbbreviation":"J. Infect. Dis.","language":"eng","author":[{"family":"Chun","given":"Helen M"},{"family":"Roediger","given":"Mollie P"},{"family":"Hullsiek","given":"Katherine Huppler"},{"family":"Thio","given":"Chloe L"},{"family":"Agan","given":"Brian K"},{"family":"Bradley","given":"William P"},{"family":"Peel","given":"Sheila A"},{"family":"Jagodzinski","given":"Linda L"},{"family":"Weintrob","given":"Amy C"},{"family":"Ganesan","given":"Anuradha"},{"family":"Wortmann","given":"Glenn"},{"family":"Crum-Cianflone","given":"Nancy F"},{"family":"Maguire","given":"Jason D"},{"family":"Landrum","given":"Michael L"},{"family":"Infectious Disease Clinical Research Program HIV Working Group","given":""}],"issued":{"date-parts":[["2012",1,15]]},"PMID":"22147794"}},{"id":381,"uris":[""],"uri":[""],"itemData":{"id":381,"type":"article-journal","title":"Hepatitis B Virus (HBV) Coinfection Accelerates Immunologic Progression in Patients With Primary HIV Infection in an Area of Hyperendemicity for HBV Infection","container-title":"The Journal of infectious diseases","source":"NCBI PubMed","DOI":"10.1093/infdis/jit299","ISSN":"1537-6613","note":"PMID: 23840045","journalAbbreviation":"J. Infect. Dis.","language":"ENG","author":[{"family":"Tsai","given":"Mao-Song"},{"family":"Chang","given":"Sui-Yuan"},{"family":"Lo","given":"Yi-Chun"},{"family":"Yang","given":"Chia-Jui"},{"family":"Sun","given":"Hsin-Yun"},{"family":"Liu","given":"Wen-Chun"},{"family":"Wu","given":"Pei-Ying"},{"family":"Hung","given":"Chien-Ching"}],"issued":{"date-parts":[["2013",8,9]]},"PMID":"23840045"}}],"schema":""} [18,19].In HCV/HIV co-infection, the HCV disease course is negatively impacted with an increased HCV viral load as compared to HCV mono-infected patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1gv9bo5vas","properties":{"formattedCitation":"{\\rtf \\super [20]\\nosupersub{}}","plainCitation":"[20]"},"citationItems":[{"id":404,"uris":[""],"uri":[""],"itemData":{"id":404,"type":"article-journal","title":"HIV-coinfection leads to a modest increase in plasma HCV-RNA load in patients with chronic HCV infection","container-title":"Antiviral research","page":"212-215","volume":"95","issue":"3","source":"NCBI PubMed","abstract":"The influence of HIV coinfection on plasma hepatitis C virus (HCV) RNA load has not been reliably evaluated. We analyzed plasma HCV RNA load in 396 HCV-monoinfected and 467 HIV/HCV-coinfected patients. Median HCV RNA concentrations (interquartile range) in HCV-monoinfected patients were 5.88 (5.3-6.2) log(10)IU/mL versus 5.96 (5.6-6.5) log(10)IU/mL in HIV/HCV-coinfected individuals (p=0.033) as determined with the Cobas Amplicor Test and 6.06 (5.4-5.7) log(10)IU/mL versus 6.3 (5.5-6.9) log(10)IU/mL (p=0.026) using the Cobas TaqMan System. The plasma HCV RNA load in patients with HIV infection and undetectable plasmatic HIV RNA was similar to that observed in HCV-monoinfected individuals [6.02 (5.45-6.61) log(10)IU/mL versus 6.01 (5.36-6.59) log(10)IU/mL, respectively (p=1.0)]. In conclusion, HIV coinfection tends to be associated with higher plasma HCV RNA load, however, the magnitude of the differences is small and this effect can be counterbalanced with antiviral therapy.","DOI":"10.1016/j.antiviral.2012.06.009","ISSN":"1872-9096","note":"PMID: 22750672","journalAbbreviation":"Antiviral Res.","language":"eng","author":[{"family":"Neukam","given":"Karin"},{"family":"García-Rey","given":"Silvia"},{"family":"Cifuentes","given":"Celia"},{"family":"Macías","given":"Juan"},{"family":"Mira","given":"José A"},{"family":"Vázquez","given":"María J"},{"family":"Parra-Sánchez","given":"Manuel"},{"family":"Palomares","given":"José C"},{"family":"Merchante","given":"Nicolás"},{"family":"Di Lello","given":"Federico A"},{"family":"Pineda","given":"Juan A"}],"issued":{"date-parts":[["2012",9]]},"PMID":"22750672"}}],"schema":""} [20] as well as accelerated fibrosis progression ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"FJND1CU8","properties":{"formattedCitation":"{\\rtf \\super [21\\uc0\\u8211{}24]\\nosupersub{}}","plainCitation":"[21–24]"},"citationItems":[{"id":301,"uris":[""],"uri":[""],"itemData":{"id":301,"type":"article-journal","title":"Liver fibrosis on account of chronic hepatitis C is more severe in HIV-positive than HIV-negative patients despite antiretroviral therapy","container-title":"Journal of viral hepatitis","page":"427-433","volume":"15","issue":"6","source":"NCBI PubMed","abstract":"The recent availability of non-invasive tools to measure liver fibrosis has allowed examination of its extent and determination of predictors in all patients with chronic hepatitis C virus (HCV) infection. On the other hand, most information on hepatic fibrosis in HCV/human immunodeficiency virus (HIV)-coinfected patients has been derived from liver biopsies taken before highly active antiretroviral therapy (HAART) was widely available. All consecutive HCV patients with elevated aminotransferases seen during the last 3 years were evaluated and liver fibrosis measured using transient elastography (FibroScan) and biochemical indexes. Patients were split according to their HIV serostatus. A total of 656 (69.6%) HCV-monoinfected and 287 (30.4%) HIV/HCV-coinfected patients were assessed. Mean CD4 count of coinfected patients was 493 cells/muL and 88% were under HAART (mean time, 4.2 +/- 2.4 years). Advanced liver fibrosis or cirrhosis was recognized in 39% of the coinfected and 18% of the monoinfected patients (P < 0.005). A good correlation was found between FibroScan) and biochemical indexes [AST to platelet ratio index (r = 0.405, P < 0.0001), FIB-4 (r = 0.393, P < 0.0001) and Forns (r = 0.407, P < 0.0001)], regardless of the HIV status. In the multivariate analysis, age >45 years, body mass index (BMI) >25 kg/m(2), and HIV infection were independently associated with advanced liver fibrosis or cirrhosis. HIV/HCV-coinfected patients have more advanced liver fibrosis than HCV-monoinfected patients despite the immunologic benefit of HAART.","DOI":"10.1111/j.1365-2893.2007.00962.x","ISSN":"1365-2893","note":"PMID: 18221303","journalAbbreviation":"J. Viral Hepat.","language":"eng","author":[{"family":"de Lédinghen","given":"V"},{"family":"Barreiro","given":"P"},{"family":"Foucher","given":"J"},{"family":"Labarga","given":"P"},{"family":"Castéra","given":"L"},{"family":"Vispo","given":"M E"},{"family":"Bernard","given":"P-H"},{"family":"Martin-Carbonero","given":"L"},{"family":"Neau","given":"D"},{"family":"García-Gascó","given":"P"},{"family":"Merrouche","given":"W"},{"family":"Soriano","given":"V"}],"issued":{"date-parts":[["2008",6]]},"PMID":"18221303"}},{"id":398,"uris":[""],"uri":[""],"itemData":{"id":398,"type":"article-journal","title":"Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis","container-title":"Journal of hepatology","page":"1-5","volume":"26","issue":"1","source":"NCBI PubMed","abstract":"BACKGROUND/AIMS: To investigate the possible role of HIV infection in the natural history of chronic parenterally-acquired hepatitis C.\nMETHODS: A multicenter cross-sectional study was performed in 547 patients with chronic parenterally-acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV-negative). Approximate duration of HCV infection was estimated in all patients included, and histologic diagnoses made at different time intervals following HCV infection were analyzed in both groups. Factors related to serum HCV-RNA levels were also investigated.\nRESULTS: Histologic findings were similar in liver biopsies from both HIV-infected and noninfected patients. However, in the first 10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar results were found in the first 5 and 15 years, respectively, and most of the HIV-negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time interval longer than 15 years. Consequently, mean interval from estimated time of HCV infection to cirrhosis was significantly longer in HIV-negative than HIV-positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with and without cirrhosis) and long duration of HCV infection were significantly associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500 cells/ml (p < 0.05).\nCONCLUSIONS: HIV infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis C viremia levels and more severe liver damage.","ISSN":"0168-8278","note":"PMID: 9147999","journalAbbreviation":"J. Hepatol.","language":"eng","author":[{"family":"Soto","given":"B"},{"family":"Sánchez-Quijano","given":"A"},{"family":"Rodrigo","given":"L"},{"family":"del Olmo","given":"J A"},{"family":"García-Bengoechea","given":"M"},{"family":"Hernández-Quero","given":"J"},{"family":"Rey","given":"C"},{"family":"Abad","given":"M A"},{"family":"Rodríguez","given":"M"},{"family":"Sales Gilabert","given":"M"},{"family":"González","given":"F"},{"family":"Mirón","given":"P"},{"family":"Caruz","given":"A"},{"family":"Relimpio","given":"F"},{"family":"Torronteras","given":"R"},{"family":"Leal","given":"M"},{"family":"Lissen","given":"E"}],"issued":{"date-parts":[["1997",1]]},"PMID":"9147999"}},{"id":400,"uris":[""],"uri":[""],"itemData":{"id":400,"type":"article-journal","title":"Impact of human immunodeficiency virus (HIV) infection on the progression of liver fibrosis in hepatitis C virus infected patients","container-title":"Gut","page":"1035-1040","volume":"52","issue":"7","source":"NCBI PubMed","abstract":"OBJECTIVES: To compare the rate of hepatic fibrosis progression in hepatitis C virus (HCV) infected and human immunodeficiency virus (HIV)-HCV coinfected patients, and to identify factors that may influence fibrosis progression.\nPATIENTS AND METHODS: A total of 153 HCV infected and 55 HCV-HIV coinfected patients were identified from two London hospitals. Eligible patients had known dates of HCV acquisition, were HCV-RNA positive, and had undergone a liver biopsy, which was graded using the Ishak score. Univariate and multivariate logistic regression analyses were used to identify factors associated with fibrosis progression rate and the development of advanced fibrosis (stages 3 and 4).\nRESULTS: The estimated median fibrosis progression rate was 0.17 units/year (interquartile range (IQR) 0.10-0.25) in HIV-HCV coinfected and 0.13 (IQR 0.07-0.17) in HCV monoinfected patients (p=0.01), equating to an estimated time from HCV infection to cirrhosis of 23 and 32 years, respectively. Older age at infection (p<0.001), HIV positivity (p=0.019), higher alanine aminotransferase (ALT) level (p=0.039), and higher inflammatory activity (p<0.001) on first biopsy were all independently associated with more rapid fibrosis progression. ALT was correlated with histological index (r=0.35, p<0.001). A CD4 cell count < or =250 x 10(6)/l was independently associated with advanced liver fibrosis (odds ratio 5.36 (95% confidence interval 1.26-22.79)) and was also correlated with a higher histological index (r=-0.42, p=0.002).\nCONCLUSION: HIV infection modifies the natural history of HCV by accelerating the rate of fibrosis progression by 1.4 fold, and the development of advanced fibrosis threefold. A low CD4 cell count was independently associated with advanced disease and correlated with higher histological index, which suggests that early antiretroviral therapy may be of benefit in slowing HCV progression in coinfected patients.","ISSN":"0017-5749","note":"PMID: 12801963","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Mohsen","given":"A H"},{"family":"Easterbrook","given":"P J"},{"family":"Taylor","given":"C"},{"family":"Portmann","given":"B"},{"family":"Kulasegaram","given":"R"},{"family":"Murad","given":"S"},{"family":"Wiselka","given":"M"},{"family":"Norris","given":"S"}],"issued":{"date-parts":[["2003",7]]},"PMID":"12801963"}},{"id":402,"uris":[""],"uri":[""],"itemData":{"id":402,"type":"article-journal","title":"Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group","container-title":"Hepatology (Baltimore, Md.)","page":"1054-1058","volume":"30","issue":"4","source":"NCBI PubMed","abstract":"The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count </=200 cells/microL, P <.0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (>50 g/d), CD4 count (</=200 cells/microL), and age at HCV infection (<25 years old) (P <. 0001, respectively) were associated with a higher fibrosis progression rate. HIV seropositivity accelerates HCV-related liver fibrosis progression. In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate.","DOI":"10.1002/hep.510300409","ISSN":"0270-9139","note":"PMID: 10498659","journalAbbreviation":"Hepatology","language":"eng","author":[{"family":"Benhamou","given":"Y"},{"family":"Bochet","given":"M"},{"family":"Di Martino","given":"V"},{"family":"Charlotte","given":"F"},{"family":"Azria","given":"F"},{"family":"Coutellier","given":"A"},{"family":"Vidaud","given":"M"},{"family":"Bricaire","given":"F"},{"family":"Opolon","given":"P"},{"family":"Katlama","given":"C"},{"family":"Poynard","given":"T"}],"issued":{"date-parts":[["1999",10]]},"PMID":"10498659"}}],"schema":""} [21–24]. Insulin resistance in HCV mono-infected patients has been associated with increased fibrosis and impaired response to treatment ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"gdZztY4y","properties":{"formattedCitation":"{\\rtf \\super [25,26]\\nosupersub{}}","plainCitation":"[25,26]"},"citationItems":[{"id":712,"uris":[""],"uri":[""],"itemData":{"id":712,"type":"article-journal","title":"Insulin resistance and hepatitis C","container-title":"World journal of gastroenterology: WJG","page":"7075-7080","volume":"12","issue":"44","source":"NCBI PubMed","abstract":"Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: \"viral\" and \"metabolic\" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARgamma receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA < or = 2 than patients with HOMA > 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 microU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.","ISSN":"1007-9327","note":"PMID: 17131467","journalAbbreviation":"World J. Gastroenterol.","language":"eng","author":[{"family":"Romero-Gómez","given":"Manuel"}],"issued":{"date-parts":[["2006",11,28]]},"PMID":"17131467"}},{"id":714,"uris":[""],"uri":[""],"itemData":{"id":714,"type":"article-journal","title":"Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis","container-title":"The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases","page":"555-563","volume":"17","issue":"5","source":"NCBI PubMed","abstract":"BACKGROUND/AIMS: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin.\nMETHODS: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software.\nRESULTS: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups.\nCONCLUSION: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype.","DOI":"10.1016/j.bjid.2013.02.009","ISSN":"1678-4391","note":"PMID: 24055394","shortTitle":"Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3","journalAbbreviation":"Braz J Infect Dis","language":"ENG","author":[{"family":"Laurito","given":"Marcela Pezzoto"},{"family":"Parise","given":"Edison Roberto"}],"issued":{"date-parts":[["2013",10]]},"PMID":"24055394"}}],"schema":""} [25,26] although in the co-infected population the impact of insulin resistance is less clear ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2n5kgfiht0","properties":{"formattedCitation":"{\\rtf \\super [27\\uc0\\u8211{}30]\\nosupersub{}}","plainCitation":"[27–30]"},"citationItems":[{"id":724,"uris":[""],"uri":[""],"itemData":{"id":724,"type":"article-journal","title":"Insulin resistance is associated with progression to hepatic fibrosis in a cohort of HIV/hepatitis C virus-coinfected patients","container-title":"AIDS (London, England)","page":"1789-1794","volume":"26","issue":"14","source":"NCBI PubMed","abstract":"OBJECTIVE: Hepatitis C virus (HCV) infection is associated with higher insulin levels and insulin resistance. We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the effect of insulin resistance on the development of hepatic fibrosis.\nMETHODS: Data were analysed from 158 nondiabetic participants in a prospective Canadian cohort of HIV/HCV-coinfected patients. Patients were defined as having insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR) index. Factors associated with a high index (HOMA-IR ≥ 2) were identified using multivariate logistic regression. Incidence rates of liver fibrosis [aspartate aminotransferase- to-platelet ratio index (APRI) ≥ 1.5] were calculated, and multivariate time-dependent Cox regression models used to assess the effect of baseline insulin resistance on the risk of developing an APRI score of at least 1.5 during follow-up.\nRESULTS: Overall, 56% had baseline HOMA-IR of at least 2. In the adjusted multivariate logistic analysis, only baseline BMI of more than 25 kg/m2 remained associated with insulin resistance [adjusted odds ratio 3.66, 95% confidence interval (CI) 1.70-7.92]. Rates of progression to significant hepatic fibrosis (APRI ≥ 1.5) were higher in those with HOMA-IR of at least 2 (16.32 per 100 person-years, 95% CI 6.68-25.97) compared with those with HOMA-IR less than 2 (7.95 per 100 person-years, 95% CI 0.16-15.75). Baseline HOMA-IR of at least 2 was associated with the development of significant fibrosis (adjusted hazard ratio 7.71, 95% CI 2.55-23.36).","DOI":"10.1097/QAD.0b013e32835612ce","ISSN":"1473-5571","note":"PMID: 22739388","journalAbbreviation":"AIDS","language":"eng","author":[{"family":"Hull","given":"Mark W"},{"family":"Rollet","given":"Kathleen"},{"family":"Moodie","given":"Erica E M"},{"family":"Walmsley","given":"Sharon"},{"family":"Cox","given":"Joseph"},{"family":"Potter","given":"Martin"},{"family":"Cooper","given":"Curtis"},{"family":"Pick","given":"Neora"},{"family":"Saeed","given":"Sahar"},{"family":"Klein","given":"Marina B"},{"family":"Canadian Co-infection Cohort Study Investigators","given":""}],"issued":{"date-parts":[["2012",9,10]]},"PMID":"22739388"}},{"id":720,"uris":[""],"uri":[""],"itemData":{"id":720,"type":"article-journal","title":"Insulin resistance impairs response to interferon plus ribavirin in patients coinfected with HIV and hepatitis C virus","container-title":"Journal of acquired immune deficiency syndromes (1999)","page":"176-181","volume":"55","issue":"2","source":"NCBI PubMed","abstract":"BACKGROUND/AIMS: Controversy exists about whether insulin resistance (IR) affects response to treatment of hepatitis C. We evaluated the effect of IR on sustained virologic response (SVR) in HIV/hepatitis C virus (HCV)-coinfected patients treated with interferon plus ribavirin.\nMETHODS: We reviewed the clinical records of HIV/HCV-coinfected patients who received interferon plus ribavirin at our institution between July 2000 and March 2007. IR was defined as a homeostasis model assessment ≥ 3.8. SVR was defined as an undetectable HCV RNA at 24 weeks after the end of treatment. Efficacy was evaluated using an on-treatment (OT) analysis. Multivariate logistic regression analysis was used to evaluate factors associated with SVR.\nRESULTS: During the study period, 218 patients were treated with interferon plus ribavirin; IR at baseline was available for 162 patients, and 134 were included in the OT analysis; HCV genotype (G) 1/4, 67%; F3-F4 fibrosis, 36%; IR 31%. SVR was achieved in 67 patients (50%) (79% in G 2/3 vs. 38% in G 1/4). IR was associated with a lower SVR [odds ratio (OR), 0.33; 95% confidence interval (CI): 0.15-0.72; P = 0.006). The independent variables related to SVR were genotype 2/3 (OR, 6.7; 95% CI: 2.71-16.98; P < 0.001), absence of IR at baseline (OR, 3.3; 95% CI: 1.36-8.26; P = 0.008), and nadir CD4 T-cell count (OR, 1.002; 95% CI: 1.00-1.00; P = 0.047).\nCONCLUSIONS: Our data suggest that IR is an important determinant of SVR in HIV/HCV-coinfected patients treated with interferon plus ribavirin. Strategies to modify IR should be explored to enhance SVR during anti-HCV therapy.","DOI":"10.1097/QAI.0b013e3181e5b1f0","ISSN":"1944-7884","note":"PMID: 20577091","journalAbbreviation":"J. Acquir. Immune Defic. Syndr.","language":"eng","author":[{"family":"Ryan","given":"Pablo"},{"family":"Resino","given":"Salvador"},{"family":"Miralles","given":"Pilar"},{"family":"Cosín","given":"Jaime"},{"family":"López","given":"Juan Carlos"},{"family":"Moreno","given":"Silvia"},{"family":"Catalán","given":"Pilar"},{"family":"Ramírez","given":"Margarita"},{"family":"Gutiérrez","given":"Isabel"},{"family":"Berenguer","given":"Juan"}],"issued":{"date-parts":[["2010",10]]},"PMID":"20577091"}},{"id":718,"uris":[""],"uri":[""],"itemData":{"id":718,"type":"article-journal","title":"Insulin resistance is not a relevant predictor of sustained virological response to pegylated interferon plus ribavirin in HIV/HCV co-infected patients","container-title":"Journal of hepatology","page":"684-692","volume":"50","issue":"4","source":"NCBI PubMed","abstract":"BACKGROUND/AIMS: To evaluate the possible influence of baseline insulin resistance in sustained virological response.\nMETHODS: One hundred and fifty-five consecutive individuals from a multicentric cohort of HIV/HCV co-infected patients who underwent therapy with pegylated interferon plus ribavirin were included. The main outcome variable was sustained virological response, defined as undetectable plasma HCV RNA at week 24 after the end of the therapy. Insulin resistance was determined using the HOMA method.\nRESULTS: Sustained virological response was achieved in 55 (36%) patients. Forty-two (38%) patients with a HOMA lower than 4 developed sustained virological response vs 13 (29%) of those with a HOMA above 4 (p=0.27). Analyses restricted to patients harbouring genotype 1 or 4 showed similar rates of sustained virological response among patients with a HOMA below and above 4 [19 (27%) vs 7 (24%); p=0.8]. In the multivariate analysis, genotype 3 [AOR 9.26; 95% CI 3.03-28.30; p<0.0001], a baseline HCV viral load below 600.000IU/mL [AOR 2.97; 95% CI 1.03-8.57; p=0.04] and baseline LDL cholesterol above 100mg/dL [AOR 6.62; 95% CI 1.97-22.19; p=0.002] were independently associated with sustained virological response.\nCONCLUSIONS: Insulin resistance is not a relevant predictor of sustained virological response to pegylated interferon plus ribavirin in HIV/HCV co-infected patients.","DOI":"10.1016/j.jhep.2008.10.032","ISSN":"1600-0641","note":"PMID: 19231001","journalAbbreviation":"J. Hepatol.","language":"eng","author":[{"family":"Merchante","given":"Nicolás"},{"family":"de los Santos-Gil","given":"Ignacio"},{"family":"Merino","given":"Dolores"},{"family":"González-Serrano","given":"Mercedes"},{"family":"Mira","given":"José A"},{"family":"Sanz-Sanz","given":"Jesús"},{"family":"Fernández-Fuertes","given":"Elisa"},{"family":"Ruiz-Morales","given":"Josefa"},{"family":"del Valle","given":"José"},{"family":"Macías","given":"Juan"},{"family":"Moro","given":"Antonio"},{"family":"Pineda","given":"Juan A"}],"issued":{"date-parts":[["2009",4]]},"PMID":"19231001"}},{"id":722,"uris":[""],"uri":[""],"itemData":{"id":722,"type":"article-journal","title":"Insulin resistance is not associated with liver fibrosis progression in HIV/hepatitis C virus-coinfected patients","container-title":"Journal of viral hepatitis","page":"449-456","volume":"13","issue":"7","source":"NCBI PubMed","abstract":"Insulin resistance (IR) is a common condition in chronic hepatitis C. Recent studies have reported that IR is associated with liver fibrosis progression in these patients. However, there is no information available on this issue in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. For these reasons, we investigate the relationship between IR and liver fibrosis in patients with HIV and HCV infections. This was a cross-sectional study where patients from an Infectious Diseases Unit with HIV/HCV coinfection who underwent a liver biopsy, with available frozen sera samples at the time of biopsy and a known or estimated date of infection were included. IR was determined by the homeostasis model assessment (HOMA-IR) method. The relationship between histological findings and several variables, including HOMA-IR values, was examined. Seventy-nine patients fulfilled the inclusion criteria. Age at HCV infection >21 years was the only variable independently associated with advanced liver fibrosis (stages F3 and F4) [adjusted odds ratio (AOR) 4.15; 95% confidence interval (CI) 1.5-11.3]. The variables associated with a fibrosis progression rate above the median were age at HCV infection >21 years (AOR 6.41; 95% CI 2.16-27.96) and previous exposure to nevirapine (AOR 8.9; 95% CI 2.01-39.36). There was no association between HOMA-IR values and the presence of advanced fibrosis or a faster fibrosis progression. Thus IR is not associated with liver damage or fibrosis progression in HIV/HCV-coinfected individuals.","DOI":"10.1111/j.1365-2893.2005.00708.x","ISSN":"1352-0504","note":"PMID: 16792538","journalAbbreviation":"J. Viral Hepat.","language":"eng","author":[{"family":"Merchante","given":"N"},{"family":"Macías","given":"J"},{"family":"Ramayo","given":"E"},{"family":"Vergara","given":"S"},{"family":"García-García","given":"J A"},{"family":"Mira","given":"J A"},{"family":"Corzo","given":"J E"},{"family":"Gómez-Mateos","given":"J M"},{"family":"Lozano","given":"F"},{"family":"Pineda","given":"J A"}],"issued":{"date-parts":[["2006",7]]},"PMID":"16792538"}}],"schema":""} [27–30]. HCV co-infected patients have increased healthcare resource utilization ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2i9ej9s0ah","properties":{"formattedCitation":"{\\rtf \\super [31]\\nosupersub{}}","plainCitation":"[31]"},"citationItems":[{"id":422,"uris":[""],"uri":[""],"itemData":{"id":422,"type":"article-journal","title":"The impact of HIV/HCV co-infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort","container-title":"Journal of viral hepatitis","page":"506-512","volume":"18","issue":"7","source":"NCBI PubMed","abstract":"HIV/hepatitis C virus (HCV) co-infection places a growing burden on the HIV/AIDS care delivery system. Evidence-based estimates of health services utilization among HIV/HCV co-infected patients can inform efficient planning. We analyzed data from the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort to estimate resource utilization and disability among HIV/HCV co-infected patients and compare them to rates seen in HIV mono-infected patients. The analysis included HIV-infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one CD4 count measured and completed at least one resource utilization data collection form (N?=?3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co-infected vs HIV mono-infected subjects. When controlling for age, sex, race, history of AIDS-defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co-infection compared to those with HIV mono-infection were 1.8 (95% CI: 1.3-2.5), 1.7 (95% CI: 1.4-2.1), and 1.6 (95% CI: 1.3-1.9) respectively. Programs serving HIV/HCV co-infected patients can expect approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono-infected patients.","DOI":"10.1111/j.1365-2893.2010.01325.x","ISSN":"1365-2893","note":"PMID: 20546501","shortTitle":"The impact of HIV/HCV co-infection on health care utilization and disability","journalAbbreviation":"J. Viral Hepat.","language":"eng","author":[{"family":"Linas","given":"B P"},{"family":"Wang","given":"B"},{"family":"Smurzynski","given":"M"},{"family":"Losina","given":"E"},{"family":"Bosch","given":"R J"},{"family":"Schackman","given":"B R"},{"family":"Rong","given":"J"},{"family":"Sax","given":"P E"},{"family":"Walensky","given":"R P"},{"family":"Schouten","given":"J"},{"family":"Freedberg","given":"K A"}],"issued":{"date-parts":[["2011",7]]},"PMID":"20546501"}}],"schema":""} [31] and increased mortality ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"24dsh4bj5o","properties":{"formattedCitation":"{\\rtf \\super [32]\\nosupersub{}}","plainCitation":"[32]"},"citationItems":[{"id":420,"uris":[""],"uri":[""],"itemData":{"id":420,"type":"article-journal","title":"Hepatitis C/HIV co-infection is associated with higher mortality in hospitalized patients with hepatitis C or HIV","container-title":"Journal of viral hepatitis","page":"720-729","volume":"17","issue":"10","source":"NCBI PubMed","abstract":"Up to 10% of all patients with Hepatitis C virus (HCV) infection are co-infected with human immunodeficiency virus (HIV); 25-30% of HIV patients are co-infected with HCV. The aim of this study was to examine the association of HCV/HIV co-infection with outcomes of hospitalized patients compared to those with HCV or HIV monoinfection. Using the 2006 Nationwide Inpatient Sample, patients with HCV or HIV monoinfection or HCV/HIV co-infection were identified using ICD-9-CM codes. We compared liver-related and infection-related admission between the three groups of patients. Multivariate logistic regression was performed to identify independent predictors of in-hospital mortality. A total of 474,843 discharges with HCV monoinfection, 206,758 with HIV monoinfection and 56,304 with HCV/HIV co-infection were included. Liver-related admissions were more common in co-infected patients (15.4%) compared to those with HIV monoinfection (3.3%, P < 0.001). Primary infectious hospitalizations were more common in HIV monoinfection (33.9%) compared to co-infected patients (26%, P < 0.001). HCV/HIV co-infection was associated with higher mortality compared to HCV monoinfection (OR 1.41, 95% CI 1.20-1.65) but not when compared to monoinfected-HIV patients. HCV-associated cirrhosis or complications thereof conferred four times greater mortality risk in patients with HIV (OR 3.96, 95% CI 3.29-4.79). The rate of hospitalization for HCV/HIV co-infected patients (23.5%) was significantly higher than those with HCV (14.8%) or HIV (19.9%) (P < 0.001). HCV/HIV co-infection is associated with significantly higher rates of hospitalization and is a risk factor for in-hospital mortality compared to patients with isolated HCV.","DOI":"10.1111/j.1365-2893.2009.01232.x","ISSN":"1365-2893","note":"PMID: 20002558","journalAbbreviation":"J. Viral Hepat.","language":"eng","author":[{"family":"Ananthakrishnan","given":"A N"},{"family":"McGinley","given":"E L"},{"family":"Fangman","given":"J"},{"family":"Saeian","given":"K"}],"issued":{"date-parts":[["2010",10]]},"PMID":"20002558"}}],"schema":""} [32] versus those living with HCV alone. Treatment of HCV is often more complex, due to the interaction between HCV and HIV medications ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"249q92fbgd","properties":{"formattedCitation":"{\\rtf \\super [33]\\nosupersub{}}","plainCitation":"[33]"},"citationItems":[{"id":406,"uris":[""],"uri":[""],"itemData":{"id":406,"type":"article-journal","title":"Focus on drug interactions: the challenge of treating hepatitis C virus infection with direct-acting antiviral drugs in the HIV-positive patient","container-title":"Current opinion in infectious diseases","page":"50-57","volume":"26","issue":"1","source":"NCBI PubMed","abstract":"PURPOSE OF REVIEW: Successful treatment of hepatitis C virus (HCV) infection is necessary for the survival of HIV-infected patients. This review covers the outcomes of current therapy, first-generation HCV direct-acting antivirals (DAAs) and their drug-to-drug interactions (DDIs). Understanding DDIs between HIV antiretroviral therapy (ART) and the DAAs in development is important to assure the best management of the HIV/HCV coinfected individuals.\nRECENT FINDINGS: The two first-in-class DAAs were approved for clinical use in 2011. The first trials with boceprevir or telaprevir added to standard therapy in HIV/HCV coinfected patients revealed triple therapy to be efficacious with significantly improved sustained virological response rates. However, these DAAs were associated with more and worse adverse effects, as well as with significant DDIs with multiple drugs, including ART. Early data on DAAs in development suggest improved efficacy and safety and the potential for lesser DDIs.\nSUMMARY: Anti-HCV therapy is fundamental in coinfected patients, but the approved therapies are suboptimal. The first-generation of approved HCV DAAs improved efficacy of therapy in coinfected patients, but have multiple safety concerns, including potentially serious drug interactions with ART. Early results from newer DAAs are promising.","DOI":"10.1097/QCO.0b013e32835c2027","ISSN":"1473-6527","note":"PMID: 23242341","shortTitle":"Focus on drug interactions","journalAbbreviation":"Curr. Opin. Infect. Dis.","language":"eng","author":[{"family":"Rodríguez-Torres","given":"Maribel"}],"issued":{"date-parts":[["2013",2]]},"PMID":"23242341"}}],"schema":""} [33]. Further complicating matters is that co-infected patients have inferior responses to interferon and ribavirin based therapy; pooled analysis showed sustained virological response rates of 38% overall with genotypes 1 and 4 being 25% and genotype 2 and 3 being 60% ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1ijd17djjt","properties":{"formattedCitation":"{\\rtf \\super [34]\\nosupersub{}}","plainCitation":"[34]"},"citationItems":[{"id":391,"uris":[""],"uri":[""],"itemData":{"id":391,"type":"article-journal","title":"Treatment outcomes of treatment-na?ve Hepatitis C patients co-infected with HIV: a systematic review and meta-analysis of observational cohorts","container-title":"PloS one","page":"e55373","volume":"8","issue":"2","source":"NCBI PubMed","abstract":"INTRODUCTION: Co-infection with Hepatitis C (HCV) and HIV is common and HIV accelerates hepatic disease progression due to HCV. However, access to HCV treatment is limited and success rates are generally poor.\nMETHODS: We conducted a systematic review and meta-analysis to assess HCV treatment outcomes in observational cohorts. Two databases (Medline and EMBASE) were searched using a compound search strategy for cohort studies reporting HCV treatment outcomes (as determined by a sustained virological response, SVR) in HIV-positive patients initiating HCV treatment for the first time.\nRESULTS: 40 studies were included for review, providing outcomes on 5339 patients from 17 countries. The pooled proportion of patients achieving SVR was 38%. Significantly poorer outcomes were observed for patients infected with HCV genotypes 1 or 4 (pooled SVR 24.5%), compared to genotypes 2 or 3 (pooled SVR 59.8%). The pooled proportion of patients who discontinued treatment due to drug toxicities (reported by 33 studies) was low, at 4.3% (3.3-5.3%). Defaulting from treatment, reported by 33 studies, was also low (5.1%, 3.5-6.6%), as was on-treatment mortality (35 studies, 0.1% (0-0.2%)).\nCONCLUSIONS: These results, reported under programmatic conditions, are comparable to those reported in randomised clinical trials, and show that although HCV treatment outcomes are generally poor in HIV co-infected patients, those infected with HCV genotypes 2 or 3 have outcomes comparable to HIV-negative patients.","DOI":"10.1371/journal.pone.0055373","ISSN":"1932-6203","note":"PMID: 23393570","shortTitle":"Treatment outcomes of treatment-na?ve Hepatitis C patients co-infected with HIV","journalAbbreviation":"PLoS ONE","language":"eng","author":[{"family":"Davies","given":"Anna"},{"family":"Singh","given":"Kasha P"},{"family":"Shubber","given":"Zara"},{"family":"Ducros","given":"Philipp"},{"family":"Mills","given":"Edward J"},{"family":"Cooke","given":"Graham"},{"family":"Ford","given":"Nathan"}],"issued":{"date-parts":[["2013"]]},"PMID":"23393570"}}],"schema":""} [34] although the addition of protease inhibitors may lead to similar responses in genotype 1 infections ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1q0q9sil7k","properties":{"formattedCitation":"{\\rtf \\super [35]\\nosupersub{}}","plainCitation":"[35]"},"citationItems":[{"id":529,"uris":[""],"uri":[""],"itemData":{"id":529,"type":"article-journal","title":"Virological response rates for telaprevir-based hepatitis C triple therapy in patients with and without HIV coinfection","container-title":"HIV medicine","source":"NCBI PubMed","abstract":"OBJECTIVES: Pegylated-interferon/ribavirin dual therapy for hepatitis C virus (HCV) infection has a lower sustained virological response (SVR) rate in HIV/HCV-coinfected patients than in HCV monoinfected patients, but little is known about the relative effectiveness of teleprevir-based triple therapy in the two groups.\nMETHODS: Data on 33 coinfected and 116 monoinfected patients were analysed on an intention-to-treat basis. SVR12 was defined as undetectable HCV RNA at week 12 post-end-of-treatment, severe anaemia as haemoglobin ≤?89?g/L or a drop of ≥?45?g/L, and advanced fibrosis/cirrhosis as Fib-4 ≥?3.25. All coinfected patients had well controlled HIV infection.\nRESULTS: The groups were similar in age, gender, percentage with Fib-4 ≥?3.25 and HCV viral load, but differed in previous treatment response, with more coinfected patients being nonresponders or treatment-intolerant (75.8% vs. 50.0% for monoinfected patients; P?<?0.01). During treatment, the percentages of patients with undetectable HCV RNA were similar, but, surprisingly, this percentage tended to be higher in coinfected patients. SVR12 rates were 60.6% in coinfected patients vs. 42.2% in monoinfected patients (P?=?0.06). In multivariable analysis, SVR12 was associated with HIV infection [odds ratio (OR) 3.55; P?<?0.01], African American race (OR 0.37; P?=?0.03) and previous treatment response (OR 0.46; P?=?0.03). Rates of severe anaemia (45.5 vs. 58.6% in coinfected and monoinfected patients, respectively; P?=?0.18) were similar in the two groups, but rash (15.2 vs. 34.5%, respectively; P?=?0.03) and rectal symptoms (12.1 vs. 43.1%, respectively; P?<?0.01) were less common in coinfected patients.\nCONCLUSIONS: Virological responses of coinfected and monoinfected patients did not differ significantly, but tended to be higher in coinfected patients, who had a 60.6% SVR12 rate. Telaprevir-based triple therapy is a promising option for coinfected patients with well-controlled HIV infection.","DOI":"10.1111/hiv.12086","ISSN":"1468-1293","note":"PMID: 24025147","journalAbbreviation":"HIV Med.","language":"ENG","author":[{"family":"Martel-Laferrière","given":"V"},{"family":"Brinkley","given":"S"},{"family":"Bichoupan","given":"K"},{"family":"Posner","given":"S"},{"family":"Stivala","given":"A"},{"family":"Perumalswami","given":"P"},{"family":"Schiano","given":"Td"},{"family":"Sulkowski","given":"M"},{"family":"Dieterich","given":"Dt"},{"family":"Branch","given":"Ad"}],"issued":{"date-parts":[["2013",9,11]]},"PMID":"24025147"}}],"schema":""} [35]. The evidence that HIV disease activity is aggravated by HCV co-infection is controversial ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"286crfmf53","properties":{"formattedCitation":"{\\rtf \\super [36]\\nosupersub{}}","plainCitation":"[36]"},"citationItems":[{"id":303,"uris":[""],"uri":[""],"itemData":{"id":303,"type":"article-journal","title":"Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy","container-title":"The Journal of infectious diseases","page":"992-1002","volume":"192","issue":"6","source":"NCBI PubMed","abstract":"OBJECTIVE: To assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of < 500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART).\nRESULTS: HCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a > or = 50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a > or = 50 cells/microL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation.\nCONCLUSIONS: HCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatus.","DOI":"10.1086/432762","ISSN":"0022-1899","note":"PMID: 16107951","journalAbbreviation":"J. Infect. Dis.","language":"eng","author":[{"family":"Rockstroh","given":"Jürgen K"},{"family":"Mocroft","given":"Amanda"},{"family":"Soriano","given":"Vincent"},{"family":"Tural","given":"Cristina"},{"family":"Losso","given":"Marcello H"},{"family":"Horban","given":"Andrzej"},{"family":"Kirk","given":"Ole"},{"family":"Phillips","given":"Andrew"},{"family":"Ledergerber","given":"Bruno"},{"family":"Lundgren","given":"Jens"},{"family":"EuroSIDA Study Group","given":""}],"issued":{"date-parts":[["2005",9,15]]},"PMID":"16107951"}}],"schema":""} [36]. Nonetheless, achieving adequate control of the HIV with the use of HAART is important as it may reduce mortality as compared to no treatment ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"r5ol0k83e","properties":{"formattedCitation":"{\\rtf \\super [37]\\nosupersub{}}","plainCitation":"[37]"},"citationItems":[{"id":393,"uris":[""],"uri":[""],"itemData":{"id":393,"type":"article-journal","title":"Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection","container-title":"Lancet","page":"1708-1713","volume":"362","issue":"9397","source":"NCBI PubMed","abstract":"BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV infection. However, replication of hepatitis C virus (HCV) is not inhibited by HAART, and treatment-related hepatotoxicity is common. To clarify the effect of HAART in HIV/HCV-coinfected patients, we studied liver-related mortality and overall mortality in 285 patients who were regularly treated during the period 1990-2002 at our department.\nMETHODS: Survival was analysed retrospectively by Kaplan-Meier and Cox's regression analyses after patients (81% haemophiliacs) had been stratified into three groups according to their antiretroviral therapy (HAART n=93, available after 1995; treatment exclusively with nucleoside analogues n=55, available after 1992; or no treatment, n=137).\nFINDINGS: Liver-related mortality rates were 0.45, 0.69, and 1.70 per 100 person-years in the HAART, antiretroviral-treatment, and untreated groups. Kaplan-Meier analysis of liver-related mortality confirmed the significant survival benefit in patients with antiretroviral therapy (p=0.018), and regression analysis identified HAART (odds ratio 0.106 [95% CI 0.020-0.564]), antiretroviral treatment (0.283 [0.103-0.780]), CD4-positive T-cell count (0.746 [0.641-0.868] per 0.05x10(9) cells/L), serum cholinesterase (0.962 [0.938-0.986] per 100 U/L), and age (1.065 [1.027-1.105] per year) as independent predictors of liver-related survival. Severe drug-related hepatotoxicity was seen in five patients treated with nucleoside analogues alone and 13 treated with HAART. No patient died from drug-related hepatotoxicity.\nINTERPRETATION: In addition to improved overall survival, antiretroviral therapy significantly reduced long-term liver-related mortality in our patients. This survival benefit seems to outweigh by far the associated risks of severe hepatotoxicity.","DOI":"10.1016/S0140-6736(03)14844-1","ISSN":"1474-547X","note":"PMID: 14643119","journalAbbreviation":"Lancet","language":"eng","author":[{"family":"Qurishi","given":"Nazifa"},{"family":"Kreuzberg","given":"Christina"},{"family":"Lüchters","given":"Guido"},{"family":"Effenberger","given":"Wolfgang"},{"family":"Kupfer","given":"Bernd"},{"family":"Sauerbruch","given":"Tilman"},{"family":"Rockstroh","given":"Jürgen K"},{"family":"Spengler","given":"Ulrich"}],"issued":{"date-parts":[["2003",11,22]]},"PMID":"14643119"}}],"schema":""} [37] and reduce the rate of fibrosis to that of a HCV mono-infected patient ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"22serj8j3t","properties":{"formattedCitation":"{\\rtf \\super [38]\\nosupersub{}}","plainCitation":"[38]"},"citationItems":[{"id":395,"uris":[""],"uri":[""],"itemData":{"id":395,"type":"article-journal","title":"Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy","container-title":"Journal of hepatology","page":"47-55","volume":"44","issue":"1","source":"NCBI PubMed","abstract":"BACKGROUND/AIMS: HIV/HCV-coinfected patients reportedly have a faster fibrosis progression rate (FPR) than HCV-monoinfected patients. This study examined whether HIV suppression through highly active antiretroviral therapy (HAART) attenuates this accelerated fibrosis progression.\nMETHODS: In two hepatitis C centers, a retrospective analysis identified 656 consecutive treatment-na?ve HCV-infected patients who had undergone a liver biopsy, had a presumed date of HCV infection, and had been tested for HIV, 274 of them HIV-positive (95.2% on HAART) and 382 HIV-negative. The primary outcome measure was the FPR, defined as Ishak fibrosis score [0-6] over estimated duration of HCV infection.\nRESULTS: Among HIV/HCV-coinfected patients, 51.2% had undetectable HIV RNA (< 400 copies/mL). There was no difference in FPR between HIV/HCV-coinfected and HCV-monoinfected patients (0.136 vs. 0.128 Ishak fibrosis units/year, P=0.29). However, HIV/HCV-coinfected patients with any detectable HIV viral load >400 copies/mL had a faster FPR (0.151) than HCV-monoinfected patients (0.128, P=0.015) and than HIV/HCV-coinfected patients with undetectable plasma HIV RNA (0.122, P=0.013) who in turn had the same FPR as HCV-monoinfected subjects (0.128, P=0.52). An accelerated FPR in HIV viremic patients was seen with CD4+ cells <500/mm(3) (0.162 vs. 0.123, undetectable HIV RNA, P=0.005) but not with CD4+ cells >500/mm(3) (0.118 vs. 0.121, P=0.89). In multivariable linear regression analysis of HIV/HCV-coinfected patients, log(10) HIV RNA level, necroinflammation, and age at HCV infection were independently correlated to FPR, but not alcohol use or CD4+ cell count (r(2)=0.45 for model).\nCONCLUSIONS: HIV/HCV-coinfected patients with undetectable HIV RNA through HAART have a slower FPR than those with any HIV RNA level and an FPR similar to HCV-monoinfected individuals.","DOI":"10.1016/j.jhep.2005.07.006","ISSN":"0168-8278","note":"PMID: 16182404","journalAbbreviation":"J. Hepatol.","language":"eng","author":[{"family":"Br?u","given":"Norbert"},{"family":"Salvatore","given":"Mirella"},{"family":"Ríos-Bedoya","given":"Carlos F"},{"family":"Fernández-Carbia","given":"Alberto"},{"family":"Paronetto","given":"Fiorenzo"},{"family":"Rodríguez-Orengo","given":"José F"},{"family":"Rodríguez-Torres","given":"Maribel"}],"issued":{"date-parts":[["2006",1]]},"PMID":"16182404"}}],"schema":""} [38] albeit may not completely achieve fibrosis regression ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"uh7s695fa","properties":{"formattedCitation":"{\\rtf \\super [39]\\nosupersub{}}","plainCitation":"[39]"},"citationItems":[{"id":408,"uris":[""],"uri":[""],"itemData":{"id":408,"type":"article-journal","title":"Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis","container-title":"AIDS (London, England)","page":"1979-1991","volume":"22","issue":"15","source":"NCBI PubMed","abstract":"OBJECTIVES: To estimate stage-specific transition probabilities in individuals coinfected with HIV and hepatitis C virus (HCV), to examine the effect of covariates on these rates, and to investigate the effect of HIV on HCV-related cirrhosis in the era of highly active antiretroviral therapy (HAART).\nDESIGN: Systematic review of natural history studies among HCV-infected individuals.\nMETHODS: Markov maximum likelihood estimation method was used to estimate stage-specific transition probabilities. A meta-analysis was performed to obtain pooled transition probabilities, and a meta-regression to investigate the impact of covariates on these rates. Risk of cirrhosis between individuals monoinfected with HCV and coinfected with HIV/HCV were compared by HAART status.\nRESULTS: The estimated mean (95% confidence intervals) annual transition probabilities of 3567 individuals coinfected with HIV/HCV (n = 17 studies) were as follows: fibrosis stage (F) F0 --> F1 0.122 (0.098-0.153); F1 --> F2 0.115 (0.095-0.140); F2 --> F3 0.124 (0.097-0.159); and F3 --> F4 0.115 (0.098-0.135) units/year. The prevalence of cirrhosis after 20 and 30 years of HCV infection was 21% (16-28%) and 49% (40-59%), respectively. Longer duration of HCV infection was significantly associated with slower rate of fibrosis progression. The overall rate ratio of cirrhosis between individuals coinfected with HIV/HCV and monoinfected with HCV (n = 27 studies) was 2.1 (1.5-3.0), 2.5 (1.8-3.4) in the non-HAART group, and 1.7 (1.1-2.8) in the HAART group.\nCONCLUSION: The rate of fibrosis progression among individuals coinfected with HIV/HCV appears constant. Our results confirm that chronic hepatitis C outcomes are worse among coinfected individuals. Over the period studied, HAART did not appear to fully correct the adverse effect of HIV infection on HCV prognosis.","DOI":"10.1097/QAD.0b013e32830e6d51","ISSN":"1473-5571","note":"PMID: 18784461","shortTitle":"Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy","journalAbbreviation":"AIDS","language":"eng","author":[{"family":"Thein","given":"Hla-Hla"},{"family":"Yi","given":"Qilong"},{"family":"Dore","given":"Gregory J"},{"family":"Krahn","given":"Murray D"}],"issued":{"date-parts":[["2008",10,1]]},"PMID":"18784461"}}],"schema":""} [39].OUTCOMES AFTER LIVER TRANSPLANTATION IN HCV/HIV CO-INFECTIONThe published outcomes of HCV/HIV co-infected patients with regards to survival and HCV recurrence were analyzed in a recent meta-analysis ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"eioPsQYM","properties":{"formattedCitation":"{\\rtf \\super [40]\\nosupersub{}}","plainCitation":"[40]"},"citationItems":[{"id":309,"uris":[""],"uri":[""],"itemData":{"id":309,"type":"article-journal","title":"Kidney and liver organ transplantation in persons with human immunodeficiency virus: An Evidence-Based Analysis","container-title":"Ontario health technology assessment series","page":"1-56","volume":"10","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVE: The objective of this analysis is to determine the effectiveness of solid organ transplantation in persons with end stage organ failure (ESOF) and human immunodeficiency virus (HIV+)\nCLINICAL NEED: CONDITION AND TARGET POPULATION Patients with end stage organ failure who have been unresponsive to other forms of treatment eventually require solid organ transplantation. Similar to persons who are HIV negative (HIV-), persons living with HIV infection (HIV+) are at risk for ESOF from viral (e.g. hepatitis B and C) and non-viral aetiologies (e.g. coronary artery disease, diabetes, hepatocellular carcinoma). Additionally, HIV+ persons also incur risks of ESOF from HIV-associated nephropathy (HIVAN), accelerated liver damage from hepatitis C virus (HCV+), with which an estimated 30% of HIV positive (HIV+) persons are co-infected, and coronary artery disease secondary to antiretroviral therapy. Concerns that the need for post transplant immunosuppression and/or the interaction of immunosuppressive drugs with antiretroviral agents may accelerate the progression of HIV disease, as well as the risk of opportunistic infections post transplantation, have led to uncertainty regarding the overall benefit of transplantation among HIV+ patients. Moreover, the scarcity of donor organs and their use in a population where the clinical benefit of transplantation is uncertain has limited the availability of organ transplantation to persons living with ESOF and HIV. With the development of highly active anti retroviral therapy (HAART), which has been available in Canada since 1997, there has been improved survival and health-related quality of life for persons living with HIV. HAART can suppress HIV replication, enhance immune function, and slow disease progression. HAART managed persons can now be expected to live longer than those in the pre-HAART era and as a result many will now experience ESOF well before they experience life-threatening conditions related to HIV infection. Given their improved prognosis and the burden of illness they may experience from ESOF, the benefit of solid organ transplantation for HIV+ patients needs to be reassessed. EVIDENCE-BASED ANALYSIS METHODS:\nRESEARCH QUESTIONS: What are the effectiveness and cost effectiveness of solid organ transplantation in HIV+ persons with ESOF?\nLITERATURE SEARCH: A literature search was performed on September 22, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1996 to September 22, 2009.\nINCLUSION CRITERIA: Systematic review with or without a Meta analysis, RCT, Non-RCT with controlsHIV+ population undergoing solid organ transplantationHIV+ population managed with HAART therapyControls include persons undergoing solid organ transplantation who are i) HIV- ii) HCV+ mono-infected, and iii) HIV+ persons with ESOF not transplanted.Studies that completed and reported results of a Kaplan-Meier Survival Curve analysis.Studies with a minimum (mean or medium) follow up of 1-year.English language citations\nEXCLUSION CRITERIA: Case reports and case series were excluded form this review.\nOUTCOMES OF INTEREST: i) Risk of Death after transplantationii) Death censored graft survival (DCGS)iii) HIV disease progression defined as the post transplant incidence of:- opportunistic infections or neoplasms,- CD4+ T-cell count < 200mm(3), and- any detectable level of plasma HIV viral load.iv) Acute graft rejection,v) Return to dialysis,vi) Recurrence of HCV infection\nSUMMARY OF FINDINGS: No direct evidence comparing an HIV+ cohort undergoing transplantation with the same not undergoing transplantation (wait list) was found in the literature search. The results of this review are reported for the following comparison cohorts undergoing transplantation: I) KIDNEY TRANSPLANTATION: HIV+ cohort compared with HIV- cohortII) LIVER TRANSPLANTATION: HIV+ cohort compared with HIV- negative cohortIII) LIVER TRANSPLANTATION: HIV+ HCV+ (co-infected) cohort compared with HCV+ (mono-infected) cohort KIDNEY TRANSPLANTATION: HIV+ VS. HIV#ENTITYSTARTX02212; Based on a pooled HIV+ cohort sample size of 285 patients across four studies, the risk of death after kidney transplantation in an HIV+ cohort does not differ to that of an HIV- cohort [hazard ratio (HR): 0.90; 95% CI: 0.36, 2.23]. The quality of evidence supporting this outcome is very low. Death censored graft survival was reported in one study with an HIV+ cohort sample size of 100, and was statistically significantly different (p=.03) to that in the HIV- cohort (n=36,492). However, the quality of evidence supporting this outcome was determined to be very low. There was also uncertainty in the rate of return to dialysis after kidney transplantation in both the HIV+ and HIV- groups and the effect, if any, this may have on patient survival. Because of the very low quality evidence rating, the effect of kidney transplantation on HIV-disease progression is uncertain. The rate of acute graft rejection was determined using the data from one study. There was a nonsignificant difference between the HIV+ and HIV- cohorts (OR 0.13; 95% CI: 0.01, 2.64), although again, because of very low quality evidence there is uncertainty in this estimate of effect. LIVER TRANSPLANTATION: HIV+ VS. HIV#ENTITYSTARTX02212; Based on a combined HIV+ cohort sample size of 198 patient across five studies, the risk of death after liver transplantation in an HIV+ cohort (with at least 50% of the cohort co-infected with HCV+) is statistically significantly 64% greater compared with an HIV- cohort (HR: 1.64; 95% CI: 1.32, 2.02). The quality of evidence supporting this outcome is very low. Death censored graft survival was reported for an HIV+ cohort in one study (n=11) however the DCGS rate of the contemporaneous control HIV- cohort was not reported. Because of sparse data the quality of evidence supporting this outcome is very low indicating death censored graft survival is uncertain. Both the CD4+ T-cell count and HIV viral load appear controlled post transplant with an incidence of opportunistic infection of 20.5%. However, the quality of this evidence for these outcomes is very low indicating uncertainty in these effects. Similarly, because of very low quality evidence there is uncertainty in the rate of acute graft rejection among both the HIV+ and HIV- groups LIVER TRANSPLANTATION: HIV+/HCV+ VS. HCV+ Based on a combined HIV+/HCV+ cohort sample size of 156 from seven studies, the risk of death after liver transplantation is significantly greater (2.8 fold) in a co-infected cohort compared with an HCV+ mono-infected cohort (HR: 2.81; 95% CI: 1.47, 5.37). The quality of evidence supporting this outcome is very low. Death censored graft survival evidence was not available. Regarding disease progression, based on a combined sample size of 71 persons in the co-infected cohort, the CD4+ T-cell count and HIV viral load appear controlled post transplant; however, again the quality of evidence supporting this outcome is very low. The rate of opportunistic infection in the co-infected cohort was 7.2%. The quality of evidence supporting this estimate is very low, indicating uncertainty in these estimates of effect. Based on a combined HIV+/HCV+ cohort (n=57) the rate of acute graft rejection does not differ to that of an HCV+ mono-infected cohort (OR: 0.88; 95% CI: 0.44, 1.76). Also based on a combined HIV+/HCV+ cohort (n=83), the rate of HCV+ recurrence does not differ to that of an HCV+ mono-infected cohort (OR: 0.66; 95% CI: 0.27, 1.59). In both cases, the quality of the supporting evidence was very low. Overall, because of very low quality evidence there is uncertainty in the effect of kidney or liver transplantation in HIV+ persons with end stage organ failure compared with those not infected with HIV. Examining the economics of this issue, the cost of kidney and liver transplants in an HIV+ patient population are, on average, 56K and 147K per case, based on both Canadian and American experiences.","ISSN":"1915-7398","note":"PMID: 23074407","shortTitle":"Kidney and liver organ transplantation in persons with human immunodeficiency virus","journalAbbreviation":"Ont Health Technol Assess Ser","language":"eng","author":[{"family":"Health Quality Ontario","given":""}],"issued":{"date-parts":[["2010"]]},"PMID":"23074407"}}],"schema":""} [40]. This analysis compared HIV/HCV co-infected patients to those infected with HCV alone. There was no difference between groups with regards to the rate of acute cellular rejection (OR = 0.88; 95%CI: 0.44-1.76) or with regards to HCV recurrence rates (OR = 0.66; 95%CI: 0.27-1.59) although the evidence quality is described as being low. A significant reduction in survival was seen in co-infected patients compared to the HCV mono-infected population (HR = 2.81; 95%CI: 1.47-5.37) although this again was based on weaker evidence overall. More recently, there have been two large prospective multicenter cohort studies examining outcomes of HCV-HIV co-infection published. In Spain, a series of 86 consecutive HCV-HIV co-infected patients were compared to a matched series of 252 HCV mono-infected patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1acma6icfg","properties":{"formattedCitation":"{\\rtf \\super [41]\\nosupersub{}}","plainCitation":"[41]"},"citationItems":[{"id":311,"uris":[""],"uri":[""],"itemData":{"id":311,"type":"article-journal","title":"Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1866-1876","volume":"12","issue":"7","source":"NCBI PubMed","abstract":"Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.","DOI":"10.1111/j.1600-6143.2012.04028.x","ISSN":"1600-6143","note":"PMID: 22471341","shortTitle":"Outcome of HCV/HIV-coinfected liver transplant recipients","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Miro","given":"J M"},{"family":"Montejo","given":"M"},{"family":"Castells","given":"L"},{"family":"Rafecas","given":"A"},{"family":"Moreno","given":"S"},{"family":"Agüero","given":"F"},{"family":"Abradelo","given":"M"},{"family":"Miralles","given":"P"},{"family":"Torre-Cisneros","given":"J"},{"family":"Pedreira","given":"J D"},{"family":"Cordero","given":"E"},{"family":"de la Rosa","given":"G"},{"family":"Moyano","given":"B"},{"family":"Moreno","given":"A"},{"family":"Perez","given":"I"},{"family":"Rimola","given":"A"},{"family":"Spanish OLT in HIV-Infected Patients Working Group investigators","given":""}],"issued":{"date-parts":[["2012",7]]},"PMID":"22471341"}}],"schema":""} [41]. Patients with HIV were eligible if they met Spanish consensus guidelines ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"vf9u24c7l","properties":{"formattedCitation":"{\\rtf \\super [42]\\nosupersub{}}","plainCitation":"[42]"},"citationItems":[{"id":313,"uris":[""],"uri":[""],"itemData":{"id":313,"type":"article-journal","title":"[GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain (March, 2005)]","container-title":"Enfermedades infecciosas y microbiología clínica","page":"353-362","volume":"23","issue":"6","source":"NCBI PubMed","abstract":"Solid organ transplant may be the only therapeutic alternative in some HIV-infected patients. Experience in North America and Europe during the last five years shows that survival at three years after an organ transplant is similar to that observed in HIV-negative patients. The criteria agreed upon to select HIV patients for transplant are: no opportunistic infections (except tuberculosis, oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4 lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver transplant) and an HIV viral load which is undetectable or suppressible with antiretroviral therapy. Another criterion is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection and the management of relapse of HCV infection, which is one of the main causes of post-liver transplant mortality. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. The English version of the manuscript is available at .","ISSN":"0213-005X","note":"PMID: 15970168","journalAbbreviation":"Enferm. Infecc. Microbiol. Clin.","language":"spa","author":[{"family":"Miró","given":"José M"},{"family":"Torre-Cisnero","given":"Julián"},{"family":"Moreno","given":"Asunción"},{"family":"Tuset","given":"Montserrat"},{"family":"Quereda","given":"Carmen"},{"family":"Laguno","given":"Montserrat"},{"family":"Vidal","given":"Elisa"},{"family":"Rivero","given":"Antonio"},{"family":"Gonzalez","given":"Juan"},{"family":"Lumbreras","given":"Carlos"},{"family":"Iribarren","given":"José A"},{"family":"Fortún","given":"Jesús"},{"family":"Rimola","given":"Antonio"},{"family":"Rafecas","given":"Antonio"},{"family":"Barril","given":"Guillermina"},{"family":"Crespo","given":"Marisa"},{"family":"Colom","given":"Joan"},{"family":"Vilardell","given":"Jordi"},{"family":"Salvador","given":"José A"},{"family":"Polo","given":"Rosa"},{"family":"Garrido","given":"Gregorio"},{"family":"Chamorro","given":"Lourdes"},{"family":"Miranda","given":"Blanca"}],"issued":{"date-parts":[["2005",7]]},"PMID":"15970168"}}],"schema":""} [42] including CD4+ T cell counts > 100 cells/L (> 200 cells/L with history of opportunistic infection), suppressed HIV viral load and no AIDS defining events other than Pneumocystis pneumonia, esophageal candidiasis or tuberculosis. In this cohort, 55% of the population had genotype 1 HCV infection and 15% were co-infected with HBV; the median model for end-stage liver disease (MELD) score at the time of transplant was 16 and the waitlist time was 4 mo. Notable differences between the HCV comparison group and the HCV/HIV co-infected group were lower rates of genotype 1 in the HCV mono-infected group, lower rates of acute rejection and lower rates of significant fibrosis (> Stage 2) with post-transplant recurrence of the HCV. Survival in the HCV/HIV co-infected group was similar in the first year (88% vs 90%) but diverged at 3 years (62% vs 76%) and 5 years post transplant (54% vs 71%). Similar rates and trends were seen for graft survival. Factors predicting poor survival on multivariate analysis included HCV genotype 1 and an increased donor risk index; having a low HCV RNA level had a significant protective effect. Low center experience was also independently associated with an increased risk of death.The main North American experience published to date is based on data from the National Institutes of Health-sponsored Solid Organ Transplantation in HIV study. This multicenter United States trial compared a group of 86 HIV/HCV co-infected patients to HCV mono-infected patients and to all transplants in patients over the age of 65 years using the United Network for Organ Sharing (UNOS) database ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1es0c7oq91","properties":{"formattedCitation":"{\\rtf \\super [2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"716-726","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.","DOI":"10.1002/lt.23411","ISSN":"1527-6473","note":"PMID: 22328294","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Terrault","given":"Norah A"},{"family":"Roland","given":"Michelle E"},{"family":"Schiano","given":"Thomas"},{"family":"Dove","given":"Lorna"},{"family":"Wong","given":"Michael T"},{"family":"Poordad","given":"Fred"},{"family":"Ragni","given":"Margaret V"},{"family":"Barin","given":"Burc"},{"family":"Simon","given":"David"},{"family":"Olthoff","given":"Kim M"},{"family":"Johnson","given":"Lynt"},{"family":"Stosor","given":"Valentina"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Fung","given":"John"},{"family":"Sherman","given":"Kenneth E"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Slakey","given":"Douglas"},{"family":"Berg","given":"Carl L"},{"family":"Carlson","given":"Laurie"},{"family":"Ferrell","given":"Linda"},{"family":"Stablein","given":"Donald M"},{"family":"Odim","given":"Jonah"},{"family":"Fox","given":"Lawrence"},{"family":"Stock","given":"Peter G"},{"family":"Solid Organ Transplantation in HIV: Multi-Site Study Investigators","given":""}],"issued":{"date-parts":[["2012",6]]},"PMID":"22328294"}}],"schema":""} [2]. Eligible patients had similar entry criteria to the Spanish study including a CD4+ T cell count > 100 cells/L for 6 months and being on a stable HAART regimen for at least 3 months with undetectable viral loads; patients intolerant to HAART were allowed entry if they were predicted to have suppression of HIV post transplant based on past medication exposure and anti-HIV drug resistance testing. There was a more liberal policy regarding opportunistic infections in that after April 2002, patients with treated opportunistic infections (excluding lymphoma, visceral Kaposi’s sarcoma, chronic cryptosporidiosis and progressive multifocal leukoencephalopathy) were eligible for enrolment in the trial.In this study, the HCV/HIV group was younger, had a lower body mass index (BMI), longer warm graft ischemic time and were more likely to have a deceased donor transplant than the HCV mono-infected group. More patients in the co-infected group received anti-HCV treatment. The co-infected group had significantly poorer survival compared to the HCV mono-infected population with 1-year survivals of 76% vs 92% and 3 year survivals of 60% vs 79%. The graft survival was also worse in HCV/HIV coinfected patients with 1-year graft survival rates of 72% vs 88% and 3 year graft survival of 53% vs 74%. The only factor identified as a risk factor for patient survival in this group was HIV infection. Risk factors for losing graft function included having a combined liver-kidney transplant (HR 3.8), BMI < 21 kg/m2 (HR 3.2), HCV+ donor (HR 2.5) and an older donor (HR 1.3/decade). Table 1 summarizes the data from the larger HCV trials published to date.Based on the literature, several major risk factors for poor transplant survival in the HCV/HIV co-infected population have been reported. These include high MELD scores ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"MMSWRVoU","properties":{"formattedCitation":"{\\rtf \\super [43,44]\\nosupersub{}}","plainCitation":"[43,44]"},"citationItems":[{"id":317,"uris":[""],"uri":[""],"itemData":{"id":317,"type":"article-journal","title":"Survival and recurrence of hepatitis C after liver transplantation in patients coinfected with human immunodeficiency virus and hepatitis C virus","container-title":"Hepatology (Baltimore, Md.)","page":"407-417","volume":"47","issue":"2","source":"NCBI PubMed","abstract":"Liver transplantation in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a recent indication. In a single center, we have compared the survival and severity of recurrent HCV infection after liver transplantation in HIV-HCV-coinfected and HCV-monoinfected patients. Seventy-nine patients receiving a first liver graft for HCV-related liver disease between 1999 and 2005 were included. Among them, 35 had highly active antiretroviral therapy-controlled HIV infection. All patients were monitored for HCV viral load and liver histology during the posttransplantation course. Coinfected patients were younger (43 +/- 6 versus 55 +/- 8 years, P < 0.0001) and had a higher Model for End-Stage Liver Disease (MELD) score (18.8 +/- 7.4 versus 14.8 +/- 4.7; P = 0.008). The 2-year and 5-year survival rates were 73% and 51% and 91% and 81% in coinfected patients and monoinfected patients, respectively (log-rank P = 0.004). Under multivariate Cox analysis, survival was related only to the MELD score (P = 0.03; risk ratio, 1.08; 95% confidence interval, 1.01, 1.15). Using the Kaplan-Meier method, the progression to fibrosis >or= F2 was significantly higher in the coinfected group (P < 0.0001).\nCONCLUSION: The results of liver transplantation in HIV-HCV-coinfected patients were satisfactory in terms of survival benefit. Earlier referral of these patients to a liver transplant unit, the use of new drugs effective against HCV, and an avoidance of drug toxicity are mandatory if we are to improve the results of this challenging indication for liver transplantation.","DOI":"10.1002/hep.21990","ISSN":"1527-3350","note":"PMID: 18098295","journalAbbreviation":"Hepatology","language":"eng","author":[{"family":"Duclos-Vallée","given":"Jean-Charles"},{"family":"Féray","given":"Cyrille"},{"family":"Sebagh","given":"Mylène"},{"family":"Teicher","given":"Elina"},{"family":"Roque-Afonso","given":"Anne-Marie"},{"family":"Roche","given":"Bruno"},{"family":"Azoulay","given":"Daniel"},{"family":"Adam","given":"René"},{"family":"Bismuth","given":"Henri"},{"family":"Castaing","given":"Denis"},{"family":"Vittecoq","given":"Daniel"},{"family":"Samuel","given":"Didier"},{"family":"THEVIC Study Group","given":""}],"issued":{"date-parts":[["2008",2]]},"PMID":"18098295"}},{"id":319,"uris":[""],"uri":[""],"itemData":{"id":319,"type":"article-journal","title":"Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"2983-2993","volume":"6","issue":"12","source":"NCBI PubMed","abstract":"Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.","DOI":"10.1111/j.1600-6143.2006.01546.x","ISSN":"1600-6135","note":"PMID: 17062005","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"de Vera","given":"M E"},{"family":"Dvorchik","given":"I"},{"family":"Tom","given":"K"},{"family":"Eghtesad","given":"B"},{"family":"Thai","given":"N"},{"family":"Shakil","given":"O"},{"family":"Marcos","given":"A"},{"family":"Demetris","given":"A"},{"family":"Jain","given":"A"},{"family":"Fung","given":"J J"},{"family":"Ragni","given":"M V"}],"issued":{"date-parts":[["2006",12]]},"PMID":"17062005"}}],"schema":""} [43,44], HCV genotype 1 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1l5vdunpuo","properties":{"formattedCitation":"{\\rtf \\super [41]\\nosupersub{}}","plainCitation":"[41]"},"citationItems":[{"id":311,"uris":[""],"uri":[""],"itemData":{"id":311,"type":"article-journal","title":"Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1866-1876","volume":"12","issue":"7","source":"NCBI PubMed","abstract":"Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.","DOI":"10.1111/j.1600-6143.2012.04028.x","ISSN":"1600-6143","note":"PMID: 22471341","shortTitle":"Outcome of HCV/HIV-coinfected liver transplant recipients","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Miro","given":"J M"},{"family":"Montejo","given":"M"},{"family":"Castells","given":"L"},{"family":"Rafecas","given":"A"},{"family":"Moreno","given":"S"},{"family":"Agüero","given":"F"},{"family":"Abradelo","given":"M"},{"family":"Miralles","given":"P"},{"family":"Torre-Cisneros","given":"J"},{"family":"Pedreira","given":"J D"},{"family":"Cordero","given":"E"},{"family":"de la Rosa","given":"G"},{"family":"Moyano","given":"B"},{"family":"Moreno","given":"A"},{"family":"Perez","given":"I"},{"family":"Rimola","given":"A"},{"family":"Spanish OLT in HIV-Infected Patients Working Group investigators","given":""}],"issued":{"date-parts":[["2012",7]]},"PMID":"22471341"}}],"schema":""} [41], African descent ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1h2pip885v","properties":{"formattedCitation":"{\\rtf \\super [44]\\nosupersub{}}","plainCitation":"[44]"},"citationItems":[{"id":319,"uris":[""],"uri":[""],"itemData":{"id":319,"type":"article-journal","title":"Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"2983-2993","volume":"6","issue":"12","source":"NCBI PubMed","abstract":"Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.","DOI":"10.1111/j.1600-6143.2006.01546.x","ISSN":"1600-6135","note":"PMID: 17062005","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"de Vera","given":"M E"},{"family":"Dvorchik","given":"I"},{"family":"Tom","given":"K"},{"family":"Eghtesad","given":"B"},{"family":"Thai","given":"N"},{"family":"Shakil","given":"O"},{"family":"Marcos","given":"A"},{"family":"Demetris","given":"A"},{"family":"Jain","given":"A"},{"family":"Fung","given":"J J"},{"family":"Ragni","given":"M V"}],"issued":{"date-parts":[["2006",12]]},"PMID":"17062005"}}],"schema":""} [44], as well as viral load ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"NcNi3iLj","properties":{"formattedCitation":"{\\rtf \\super [41,44]\\nosupersub{}}","plainCitation":"[41,44]"},"citationItems":[{"id":311,"uris":[""],"uri":[""],"itemData":{"id":311,"type":"article-journal","title":"Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1866-1876","volume":"12","issue":"7","source":"NCBI PubMed","abstract":"Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.","DOI":"10.1111/j.1600-6143.2012.04028.x","ISSN":"1600-6143","note":"PMID: 22471341","shortTitle":"Outcome of HCV/HIV-coinfected liver transplant recipients","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Miro","given":"J M"},{"family":"Montejo","given":"M"},{"family":"Castells","given":"L"},{"family":"Rafecas","given":"A"},{"family":"Moreno","given":"S"},{"family":"Agüero","given":"F"},{"family":"Abradelo","given":"M"},{"family":"Miralles","given":"P"},{"family":"Torre-Cisneros","given":"J"},{"family":"Pedreira","given":"J D"},{"family":"Cordero","given":"E"},{"family":"de la Rosa","given":"G"},{"family":"Moyano","given":"B"},{"family":"Moreno","given":"A"},{"family":"Perez","given":"I"},{"family":"Rimola","given":"A"},{"family":"Spanish OLT in HIV-Infected Patients Working Group investigators","given":""}],"issued":{"date-parts":[["2012",7]]},"PMID":"22471341"}},{"id":319,"uris":[""],"uri":[""],"itemData":{"id":319,"type":"article-journal","title":"Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"2983-2993","volume":"6","issue":"12","source":"NCBI PubMed","abstract":"Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.","DOI":"10.1111/j.1600-6143.2006.01546.x","ISSN":"1600-6135","note":"PMID: 17062005","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"de Vera","given":"M E"},{"family":"Dvorchik","given":"I"},{"family":"Tom","given":"K"},{"family":"Eghtesad","given":"B"},{"family":"Thai","given":"N"},{"family":"Shakil","given":"O"},{"family":"Marcos","given":"A"},{"family":"Demetris","given":"A"},{"family":"Jain","given":"A"},{"family":"Fung","given":"J J"},{"family":"Ragni","given":"M V"}],"issued":{"date-parts":[["2006",12]]},"PMID":"17062005"}}],"schema":""} [41,44]. Few studies have looked at factors impacting graft survival; Terrault et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"tspirnl9f","properties":{"formattedCitation":"{\\rtf \\super [2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"716-726","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.","DOI":"10.1002/lt.23411","ISSN":"1527-6473","note":"PMID: 22328294","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Terrault","given":"Norah A"},{"family":"Roland","given":"Michelle E"},{"family":"Schiano","given":"Thomas"},{"family":"Dove","given":"Lorna"},{"family":"Wong","given":"Michael T"},{"family":"Poordad","given":"Fred"},{"family":"Ragni","given":"Margaret V"},{"family":"Barin","given":"Burc"},{"family":"Simon","given":"David"},{"family":"Olthoff","given":"Kim M"},{"family":"Johnson","given":"Lynt"},{"family":"Stosor","given":"Valentina"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Fung","given":"John"},{"family":"Sherman","given":"Kenneth E"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Slakey","given":"Douglas"},{"family":"Berg","given":"Carl L"},{"family":"Carlson","given":"Laurie"},{"family":"Ferrell","given":"Linda"},{"family":"Stablein","given":"Donald M"},{"family":"Odim","given":"Jonah"},{"family":"Fox","given":"Lawrence"},{"family":"Stock","given":"Peter G"},{"family":"Solid Organ Transplantation in HIV: Multi-Site Study Investigators","given":""}],"issued":{"date-parts":[["2012",6]]},"PMID":"22328294"}}],"schema":""} [2] identified that receiving either a HCV+ graft or an older organ, undergoing a simultaneous liver-kidney transplant or being underweight decreased graft survival. Fibrosing cholestatic hepatitis (FCH), an often fatal complication of hepatitis C post transplant is relatively uncommon in the mono-infected population with an incidence of about 5%-8% ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"TCY93G6x","properties":{"formattedCitation":"{\\rtf \\super [41,45,46]\\nosupersub{}}","plainCitation":"[41,45,46]"},"citationItems":[{"id":321,"uris":[""],"uri":[""],"itemData":{"id":321,"type":"article-journal","title":"Clinical characterization of patients developing histologically-proven fibrosing cholestatic hepatitis C post-liver transplantation","container-title":"Hepatology research: the official journal of the Japan Society of Hepatology","page":"328-339","volume":"41","issue":"4","source":"NCBI PubMed","abstract":"Aim:? Fibrosing cholestatic hepatitis C (FCH) post-liver transplantation (LT) is an uncommon disorder with extremely poor outcome. Using stringent histological criteria, we sought to identify cases of FCH to better characterize its incidence, clinical features and outcomes. Methods:? From January 1991 to December 2007, 973 LT for hepatitis C virus (HCV) were performed at our center. Using the pathology database, 51 cases with a provisional diagnosis of FCH were identified. FCH was diagnosed histologically by cholestasis accompanied by thin periportal fibrous septa, ductular reaction and mild inflammation. Results:? FCH was reconfirmed in 24 recipients; seven had concurrent biliary problems. Twenty-seven cases were excluded; biopsy was unavailable in nine cases, 15 did not meet the histological criteria of FCH and three had missing clinical information. All received deceased donors at a mean age of 64.4?years (15/17 aged >50?years). Mean time from LT to FCH was 7.6?months with 16 of 17 diagnosed within 1?year of LT. At diagnosis, mean viral load was 14.4?million IU/mL, bilirubin 16.2?mg/dL, aspartate aminotransferase 262?IU/mL, alanine aminotransferase 192?IU/mL and alkaline phosphatase 299?IU/mL. All 17 patients died or required re-LT a mean of 7.8?months after the FCH diagnosis. Conclusion:? FCH occurs infrequently and is typified by hyperbilirubinemia, donor age of more than 50?years, extremely high HCV RNA and specific histological changes occurring within the first several months post-LT with extremely poor patient and graft survival. Histology alone is not reliable for the diagnosis of FCH, especially in the setting of recurrent HCV with concurrent biliary problems.","DOI":"10.1111/j.1872-034X.2011.00781.x","ISSN":"1386-6346","note":"PMID: 21426450","journalAbbreviation":"Hepatol. Res.","language":"eng","author":[{"family":"Satapathy","given":"Sanjaya K"},{"family":"Sclair","given":"Seth"},{"family":"Fiel","given":"M Isabel"},{"family":"Del Rio Martin","given":"Juan"},{"family":"Schiano","given":"Thomas"}],"issued":{"date-parts":[["2011",4]]},"PMID":"21426450"}},{"id":323,"uris":[""],"uri":[""],"itemData":{"id":323,"type":"article-journal","title":"Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation","container-title":"Hepatology (Baltimore, Md.)","page":"971-976","volume":"23","issue":"5","source":"NCBI PubMed","abstract":"Recurrent infection with hepatitis C virus (HCV) is almost universal following orthotopic liver transplantation although clinical severity varies. Data on 135 patients who underwent transplantation for hepatitis C cirrhosis were reviewed. We describe a progressive, severe cholestatic form of hepatitis occurring in a subgroup of patients with recurrent hepatitis C. Ten patients with severe recurrent hepatitis C were identified; 1 has died, 1 awaits retransplantation, and 8 have undergone retransplantation. All 10 developed severe progressive cholestatic hepatitis, with a mean rise in bilirubin to 24.7 mg/dL at the time of retransplantation. Histology at initial recurrence was of mild hepatitis without evidence of rejection. The failed grafts showed either cirrhosis or confluent hepatic necrosis. The onset of cholestasis preceded retransplantation by less than 5 months. Our study suggests that a minority of patients with recurrent hepatitis C after undergoing liver transplantation develop a severe progressive cholestatic hepatitis and liver failure.","DOI":"10.1002/hep.510230505","ISSN":"0270-9139","note":"PMID: 8621177","journalAbbreviation":"Hepatology","language":"eng","author":[{"family":"Schluger","given":"L K"},{"family":"Sheiner","given":"P A"},{"family":"Thung","given":"S N"},{"family":"Lau","given":"J Y"},{"family":"Min","given":"A"},{"family":"Wolf","given":"D C"},{"family":"Fiel","given":"I"},{"family":"Zhang","given":"D"},{"family":"Gerber","given":"M A"},{"family":"Miller","given":"C M"},{"family":"Bodenheimer","given":"H C, Jr"}],"issued":{"date-parts":[["1996",5]]},"PMID":"8621177"}},{"id":311,"uris":[""],"uri":[""],"itemData":{"id":311,"type":"article-journal","title":"Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1866-1876","volume":"12","issue":"7","source":"NCBI PubMed","abstract":"Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.","DOI":"10.1111/j.1600-6143.2012.04028.x","ISSN":"1600-6143","note":"PMID: 22471341","shortTitle":"Outcome of HCV/HIV-coinfected liver transplant recipients","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Miro","given":"J M"},{"family":"Montejo","given":"M"},{"family":"Castells","given":"L"},{"family":"Rafecas","given":"A"},{"family":"Moreno","given":"S"},{"family":"Agüero","given":"F"},{"family":"Abradelo","given":"M"},{"family":"Miralles","given":"P"},{"family":"Torre-Cisneros","given":"J"},{"family":"Pedreira","given":"J D"},{"family":"Cordero","given":"E"},{"family":"de la Rosa","given":"G"},{"family":"Moyano","given":"B"},{"family":"Moreno","given":"A"},{"family":"Perez","given":"I"},{"family":"Rimola","given":"A"},{"family":"Spanish OLT in HIV-Infected Patients Working Group investigators","given":""}],"issued":{"date-parts":[["2012",7]]},"PMID":"22471341"}}],"schema":""} [41,45,46]. The incidence is increased in the co-infected population by two to three fold with the largest series suggesting a prevalence of 19% ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8rlYnsOq","properties":{"formattedCitation":"{\\rtf \\super [41,44,47]\\nosupersub{}}","plainCitation":"[41,44,47]"},"citationItems":[{"id":325,"uris":[""],"uri":[""],"itemData":{"id":325,"type":"article-journal","title":"Fibrosing cholestatic hepatitis in HIV/HCV co-infected transplant patients-usefulness of early markers after liver transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1686-1695","volume":"11","issue":"8","source":"NCBI PubMed","abstract":"We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.","DOI":"10.1111/j.1600-6143.2011.03608.x","ISSN":"1600-6143","note":"PMID: 21749638","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Antonini","given":"T M"},{"family":"Sebagh","given":"M"},{"family":"Roque-Afonso","given":"A M"},{"family":"Teicher","given":"E"},{"family":"Roche","given":"B"},{"family":"Sobesky","given":"R"},{"family":"Coilly","given":"A"},{"family":"Vaghefi","given":"P"},{"family":"Adam","given":"R"},{"family":"Vittecoq","given":"D"},{"family":"Castaing","given":"D"},{"family":"Samuel","given":"D"},{"family":"Duclos-Vallée","given":"J-C"}],"issued":{"date-parts":[["2011",8]]},"PMID":"21749638"}},{"id":311,"uris":[""],"uri":[""],"itemData":{"id":311,"type":"article-journal","title":"Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1866-1876","volume":"12","issue":"7","source":"NCBI PubMed","abstract":"Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.","DOI":"10.1111/j.1600-6143.2012.04028.x","ISSN":"1600-6143","note":"PMID: 22471341","shortTitle":"Outcome of HCV/HIV-coinfected liver transplant recipients","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Miro","given":"J M"},{"family":"Montejo","given":"M"},{"family":"Castells","given":"L"},{"family":"Rafecas","given":"A"},{"family":"Moreno","given":"S"},{"family":"Agüero","given":"F"},{"family":"Abradelo","given":"M"},{"family":"Miralles","given":"P"},{"family":"Torre-Cisneros","given":"J"},{"family":"Pedreira","given":"J D"},{"family":"Cordero","given":"E"},{"family":"de la Rosa","given":"G"},{"family":"Moyano","given":"B"},{"family":"Moreno","given":"A"},{"family":"Perez","given":"I"},{"family":"Rimola","given":"A"},{"family":"Spanish OLT in HIV-Infected Patients Working Group investigators","given":""}],"issued":{"date-parts":[["2012",7]]},"PMID":"22471341"}},{"id":319,"uris":[""],"uri":[""],"itemData":{"id":319,"type":"article-journal","title":"Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"2983-2993","volume":"6","issue":"12","source":"NCBI PubMed","abstract":"Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.","DOI":"10.1111/j.1600-6143.2006.01546.x","ISSN":"1600-6135","note":"PMID: 17062005","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"de Vera","given":"M E"},{"family":"Dvorchik","given":"I"},{"family":"Tom","given":"K"},{"family":"Eghtesad","given":"B"},{"family":"Thai","given":"N"},{"family":"Shakil","given":"O"},{"family":"Marcos","given":"A"},{"family":"Demetris","given":"A"},{"family":"Jain","given":"A"},{"family":"Fung","given":"J J"},{"family":"Ragni","given":"M V"}],"issued":{"date-parts":[["2006",12]]},"PMID":"17062005"}}],"schema":""} [41,44,47]. Commonly associated factors for FCH in the mono-infected population including acute rejection and older donor age ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1abe1d5ng2","properties":{"formattedCitation":"{\\rtf \\super [48]\\nosupersub{}}","plainCitation":"[48]"},"citationItems":[{"id":331,"uris":[""],"uri":[""],"itemData":{"id":331,"type":"article-journal","title":"Cholestatic hepatitis C following liver transplantation: an outcome-based histological definition, clinical predictors, and prognosis","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"78-88","volume":"19","issue":"1","source":"NCBI PubMed","abstract":"Cholestatic hepatitis C virus (HCV) is a rare form of recurrent HCV following liver transplantation (LT) without specific diagnostic criteria. An outcome-based method to improve its diagnosis and a description of its prognosis are needed. All 1-year post-LT protocol liver biopsy samples and biopsy samples initially reported to show cholestatic HCV from patients transplanted with HCV between February 2002 and December 2009 were reviewed for the inflammation grade, the fibrosis stage, and 4 cholestatic HCV features: ductular proliferation, canalicular cholestasis with or without intracellular cholestasis, hepatocyte swelling with or without lobular disarray, and sinusoidal/pericellular fibrosis. We used patient and graft survival to define histological criteria for cholestatic HCV, and compared the clinical features of these patients to those of patients with minimal or significant post-LT fibrosis. One hundred seventy-nine patients were analyzed, the median age was 56 years, and 73% were male. Patients with 3 or more of the 4 cholestatic HCV criteria had significantly worse survival (log-rank P < 0.001) regardless of the fibrosis stage, and this was used as our novel definition of cholestatic HCV. Using this definition, we found that 27 patients (15%) had cholestatic HCV, 53 (30%) had significant fibrosis (stage ≥ 2/4), and 99 (55%) had minimal fibrosis (stage < 2/4). The final model for clinical predictors of cholestatic HCV included donor age [odds ratio (OR) = 1.37 per decade, P = 0.04] and previous rejection (Banff grade ≥ 5; OR = 4.19, P = 0.002). Total bilirubin was the strongest laboratory predictor of cholestatic HCV (area under the curve = 0.93), whereas the HCV viral load was not a significant predictor. The final model of post-LT survival included the pathology group {cholestatic HCV [hazard ratio (HR) = 6.07, P < 0.001] and significant fibrosis (HR = 2.53, P = 0.02)}, donor age (HR = 1.49 per decade, P < 0.001), and cold ischemia time (HR = 1.11 per hour, P = 0.02). In conclusion, we propose diagnostic criteria for cholestatic HCV that include specific criteria (the presence of at least 3 of the 4 histopathological features on biopsy) and other supportive and exclusionary criteria. Older donor age and rejection increase the risk of cholestatic HCV, and an elevation in the total bilirubin level may help to identify these patients. These criteria must be validated prospectively.","DOI":"10.1002/lt.23559","ISSN":"1527-6473","note":"PMID: 23081888","shortTitle":"Cholestatic hepatitis C following liver transplantation","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Verna","given":"Elizabeth C"},{"family":"Abdelmessih","given":"Rita"},{"family":"Salomao","given":"Marcela A"},{"family":"Lefkowitch","given":"Jay"},{"family":"Moreira","given":"Roger K"},{"family":"Brown","given":"Robert S, Jr"}],"issued":{"date-parts":[["2013",1]]},"PMID":"23081888"}}],"schema":""} [48] were not identified as predictors in the co-infected population ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1gul46sgui","properties":{"formattedCitation":"{\\rtf \\super [47]\\nosupersub{}}","plainCitation":"[47]"},"citationItems":[{"id":325,"uris":[""],"uri":[""],"itemData":{"id":325,"type":"article-journal","title":"Fibrosing cholestatic hepatitis in HIV/HCV co-infected transplant patients-usefulness of early markers after liver transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1686-1695","volume":"11","issue":"8","source":"NCBI PubMed","abstract":"We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.","DOI":"10.1111/j.1600-6143.2011.03608.x","ISSN":"1600-6143","note":"PMID: 21749638","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Antonini","given":"T M"},{"family":"Sebagh","given":"M"},{"family":"Roque-Afonso","given":"A M"},{"family":"Teicher","given":"E"},{"family":"Roche","given":"B"},{"family":"Sobesky","given":"R"},{"family":"Coilly","given":"A"},{"family":"Vaghefi","given":"P"},{"family":"Adam","given":"R"},{"family":"Vittecoq","given":"D"},{"family":"Castaing","given":"D"},{"family":"Samuel","given":"D"},{"family":"Duclos-Vallée","given":"J-C"}],"issued":{"date-parts":[["2011",8]]},"PMID":"21749638"}}],"schema":""} [47].OUTCOMES AFTER LIVER TRANSPLANTATION IN HBV AND HIV CO-INFECTIONIn general, the results for HBV/HIV co-infected patients are very good and are similar to that of HBV mono-infected patients. One of the largest published series of HBV/HIV co-infected patients undergoing transplant consists of 22 patients predominantly from the Solid Organ Transplantation in HIV Multi-Site Study ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"22so3o12h1","properties":{"formattedCitation":"{\\rtf \\super [49]\\nosupersub{}}","plainCitation":"[49]"},"citationItems":[{"id":333,"uris":[""],"uri":[""],"itemData":{"id":333,"type":"article-journal","title":"Virologic and clinical outcomes of hepatitis B virus infection in HIV-HBV coinfected transplant recipients","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1268-1275","volume":"10","issue":"5","source":"NCBI PubMed","abstract":"Liver transplantation (LT) is the treatment of choice for end-stage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-hepatitis B virus (HBV) coinfected patients transplanted between 2001-2007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/mL, range 9-789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% versus 85% in HBV mono- versus coinfected patients (p = 0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low-level HBV DNA is detectable in approximately 50% of recipients.","DOI":"10.1111/j.1600-6143.2010.03070.x","ISSN":"1600-6143","note":"PMID: 20346065","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Coffin","given":"C S"},{"family":"Stock","given":"P G"},{"family":"Dove","given":"L M"},{"family":"Berg","given":"C L"},{"family":"Nissen","given":"N N"},{"family":"Curry","given":"M P"},{"family":"Ragni","given":"M"},{"family":"Regenstein","given":"F G"},{"family":"Sherman","given":"K E"},{"family":"Roland","given":"M E"},{"family":"Terrault","given":"N A"}],"issued":{"date-parts":[["2010",5]]},"PMID":"20346065"}}],"schema":""} [49]. Patients were required to have either undetectable HIV viral loads or be predictably suppressible, CD4+ T cell count > 100 cells/L, absence of prior opportunistic infections and no history of visceral Kaposi’s sarcoma. Post transplantation, patients received a combination of hepatitis B immune globulin (HBIG) and antiviral therapy with indefinite use of HBIG targeting anti-HBs titers of > 100 IU/L; HBV antiviral treatment was based on their treatment prior to transplant. Co-infected patients were compared to patients with HBV undergoing transplantation at the University of California, San Francisco. Overall, the co-infected group was younger (median age 47 years vs 58 years), included more males (100% vs 65%) and fewer were transplanted for HCC as a primary indication (9% vs 25%). Both groups had similar donor characteristics other than the co-infected group receiving younger donors (39 years vs 51 years); immunosuppression regimens in the co-infected population were more likely to use cyclosporine and less likely to be receiving mycophenolate mofetil. The three-year survival of 85% was not significantly different to the HBV mono-infected population; there was no evidence of HBV disease activity in either group. Similar positive outcomes have been seen in other small trials (Table 2).ECONOMIC STUDIES OF CO-INFECTED LIVER TRANPLANTATIONLiver transplant has significant cost to payers with estimated costs of transplant in the HCV mono-infected population of $169000 USD initially and subsequent annual costs of $38000 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2jgunbr0r0","properties":{"formattedCitation":"{\\rtf \\super [50]\\nosupersub{}}","plainCitation":"[50]"},"citationItems":[{"id":702,"uris":[""],"uri":[""],"itemData":{"id":702,"type":"article-journal","title":"All-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States: a managed care perspective","container-title":"Journal of managed care pharmacy: JMCP","page":"531-546","volume":"17","issue":"7","source":"NCBI PubMed","abstract":"BACKGROUND: Approximately 3.2-3.9 million U.S. residents are infected with the hepatitis C virus (HCV). Total annual costs (direct and indirect) in the United States for HCV were estimated to be $5.46 billion in 1997, and direct medical costs have been predicted to increase to $10.7 billion for the 10-year period from 2010 through 2019, due in part to the increasing number of HCV patients developing advanced liver disease (AdvLD).\nOBJECTIVE: To quantify in a sample of commercially insured enrollees (a) total per patient per year (PPPY) all-cause costs to the payer, overall and by the stage of liver disease, for patients diagnosed with HCV; and (b) incremental all-cause costs for patients diagnosed with HCV relative to a matched non-HCV cohort.\nMETHODS: This retrospective, matched cohort study included patients aged at least 18 years and with at least 6 months of continuous enrollment in a large managed care organization (MCO) claims database from July 1, 2001, through March 31, 2010. Patients with a diagnosis of HCV (ICD-9-CM codes 070.54, 070.70) were identified and stratified into those with and without AdvLD, defined as decompensated cirrhosis (ICD-9-CM codes 070.44, 070.71, 348.3x, 456.0, 456.1, 456.2x, 572.2, 572.3, 572.4, 782.4, 789.59); hepatocellular carcinoma (HCC, ICD-9-CM code 155); or liver transplant (ICD-9-CM codes V42.7, 50.5 or CPT codes 47135, 47136). For patients without AdvLD, the index date was the first HCV diagnosis date observed at least 6 months after the first enrollment date, and at least 6 months of continuous enrollment after the index date were required. HCV patients without AdvLD were stratified into those with and without compensated cirrhosis (ICD-9-CM codes 571.2, 571.5, 571.6). For patients with AdvLD, the index date was the date of the first AdvLD diagnosis observed at least 6 months after the first enrollment date, and at least 1 day of enrollment after the index date was required. Cases were matched in an approximate 1:10 ratio to comparison patients without an HCV diagnosis or AdvLD diagnosis who met all other inclusion criteria based on gender, age, hospital referral region state, pre-index health care costs, alcoholism, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and a modified Charlson Comorbidity Index. For the HCV and comparison patient cohorts, PPPY all-cause costs to the payer were calculated as total allowed charges summed across all patients divided by total patient-days of follow-up for the cohort, multiplied by 365, inflation-normalized to 2009 dollars. Because the calculation of PPPY cost generated a single value for each cohort, bootstrapping was used to generate descriptive statistics. Incremental PPPY costs for HCV patients relative to non-HCV patients were calculated as between-group differences in PPPY costs. T-tests for independent samples were used to compare costs between case and comparison cohorts.\nRESULTS: A total of 34,597 patients diagnosed with HCV, 78.0% with HCV without AdvLD, 4.4% with compensated cirrhosis, 12.3% with decompensated cirrhosis, 2.8% with HCC, and 2.6% with liver transplant, were matched to 330,435 comparison patients. Mean (SD) age of all HCV cases was 49.9 (8.5) years; 61.7% were male. Incremental mean (SD) PPPY costs in 2009 dollars for all HCV patients relative to comparison patients were $ 9,681 ($176) PPPY. Incremental PPPY costs were $5,870 ($157) and $5,330 ($491) for HCV patients without liver disease and with compensated cirrhosis, respectively. Incremental PPPY costs for patients with AdvLD were $27,845 ($ 965) for decompensated cirrhosis, $43,671 ($2,588) for HCC, and $ 93,609 ($4,482) for transplant. Incremental prescription drug costs, including the cost of antiviral drugs, were $2,739 ($37) for HCV patients overall, $2,659 ($41) for HCV without liver involvement, and $3,102 ($157) for HCV with compensated cirrhosis. These between-group differences were statistically significant at P<0.001.\nCONCLUSIONS: Based on a retrospective analysis of data from a large, MCO claims database, patients diagnosed with HCV had annual all-cause medical costs that were almost twice as high as those of enrollees without a diagnosis of HCV. Health care costs increased dramatically with AdvLD. Data from this study may help MCOs project future HCV costs and facilitate planning for HCV patient management efforts.","ISSN":"1944-706X","note":"PMID: 21870894","shortTitle":"All-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States","journalAbbreviation":"J Manag Care Pharm","language":"eng","author":[{"family":"McAdam-Marx","given":"Carrie"},{"family":"McGarry","given":"Lisa J"},{"family":"Hane","given":"Christopher A"},{"family":"Biskupiak","given":"Joseph"},{"family":"Deniz","given":"Baris"},{"family":"Brixner","given":"Diana I"}],"issued":{"date-parts":[["2011",9]]},"PMID":"21870894"}}],"schema":""} [50]. Very limited study has been done on the economic impact of HIV on the cost of transplantation. One study estimated that the presence of HIV adds an additional cost of approximately $38000 to the cost of liver transplantation ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"82lokpv2m","properties":{"formattedCitation":"{\\rtf \\super [40]\\nosupersub{}}","plainCitation":"[40]"},"citationItems":[{"id":309,"uris":[""],"uri":[""],"itemData":{"id":309,"type":"article-journal","title":"Kidney and liver organ transplantation in persons with human immunodeficiency virus: An Evidence-Based Analysis","container-title":"Ontario health technology assessment series","page":"1-56","volume":"10","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVE: The objective of this analysis is to determine the effectiveness of solid organ transplantation in persons with end stage organ failure (ESOF) and human immunodeficiency virus (HIV+)\nCLINICAL NEED: CONDITION AND TARGET POPULATION Patients with end stage organ failure who have been unresponsive to other forms of treatment eventually require solid organ transplantation. Similar to persons who are HIV negative (HIV-), persons living with HIV infection (HIV+) are at risk for ESOF from viral (e.g. hepatitis B and C) and non-viral aetiologies (e.g. coronary artery disease, diabetes, hepatocellular carcinoma). Additionally, HIV+ persons also incur risks of ESOF from HIV-associated nephropathy (HIVAN), accelerated liver damage from hepatitis C virus (HCV+), with which an estimated 30% of HIV positive (HIV+) persons are co-infected, and coronary artery disease secondary to antiretroviral therapy. Concerns that the need for post transplant immunosuppression and/or the interaction of immunosuppressive drugs with antiretroviral agents may accelerate the progression of HIV disease, as well as the risk of opportunistic infections post transplantation, have led to uncertainty regarding the overall benefit of transplantation among HIV+ patients. Moreover, the scarcity of donor organs and their use in a population where the clinical benefit of transplantation is uncertain has limited the availability of organ transplantation to persons living with ESOF and HIV. With the development of highly active anti retroviral therapy (HAART), which has been available in Canada since 1997, there has been improved survival and health-related quality of life for persons living with HIV. HAART can suppress HIV replication, enhance immune function, and slow disease progression. HAART managed persons can now be expected to live longer than those in the pre-HAART era and as a result many will now experience ESOF well before they experience life-threatening conditions related to HIV infection. Given their improved prognosis and the burden of illness they may experience from ESOF, the benefit of solid organ transplantation for HIV+ patients needs to be reassessed. EVIDENCE-BASED ANALYSIS METHODS:\nRESEARCH QUESTIONS: What are the effectiveness and cost effectiveness of solid organ transplantation in HIV+ persons with ESOF?\nLITERATURE SEARCH: A literature search was performed on September 22, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1996 to September 22, 2009.\nINCLUSION CRITERIA: Systematic review with or without a Meta analysis, RCT, Non-RCT with controlsHIV+ population undergoing solid organ transplantationHIV+ population managed with HAART therapyControls include persons undergoing solid organ transplantation who are i) HIV- ii) HCV+ mono-infected, and iii) HIV+ persons with ESOF not transplanted.Studies that completed and reported results of a Kaplan-Meier Survival Curve analysis.Studies with a minimum (mean or medium) follow up of 1-year.English language citations\nEXCLUSION CRITERIA: Case reports and case series were excluded form this review.\nOUTCOMES OF INTEREST: i) Risk of Death after transplantationii) Death censored graft survival (DCGS)iii) HIV disease progression defined as the post transplant incidence of:- opportunistic infections or neoplasms,- CD4+ T-cell count < 200mm(3), and- any detectable level of plasma HIV viral load.iv) Acute graft rejection,v) Return to dialysis,vi) Recurrence of HCV infection\nSUMMARY OF FINDINGS: No direct evidence comparing an HIV+ cohort undergoing transplantation with the same not undergoing transplantation (wait list) was found in the literature search. The results of this review are reported for the following comparison cohorts undergoing transplantation: I) KIDNEY TRANSPLANTATION: HIV+ cohort compared with HIV- cohortII) LIVER TRANSPLANTATION: HIV+ cohort compared with HIV- negative cohortIII) LIVER TRANSPLANTATION: HIV+ HCV+ (co-infected) cohort compared with HCV+ (mono-infected) cohort KIDNEY TRANSPLANTATION: HIV+ VS. HIV#ENTITYSTARTX02212; Based on a pooled HIV+ cohort sample size of 285 patients across four studies, the risk of death after kidney transplantation in an HIV+ cohort does not differ to that of an HIV- cohort [hazard ratio (HR): 0.90; 95% CI: 0.36, 2.23]. The quality of evidence supporting this outcome is very low. Death censored graft survival was reported in one study with an HIV+ cohort sample size of 100, and was statistically significantly different (p=.03) to that in the HIV- cohort (n=36,492). However, the quality of evidence supporting this outcome was determined to be very low. There was also uncertainty in the rate of return to dialysis after kidney transplantation in both the HIV+ and HIV- groups and the effect, if any, this may have on patient survival. Because of the very low quality evidence rating, the effect of kidney transplantation on HIV-disease progression is uncertain. The rate of acute graft rejection was determined using the data from one study. There was a nonsignificant difference between the HIV+ and HIV- cohorts (OR 0.13; 95% CI: 0.01, 2.64), although again, because of very low quality evidence there is uncertainty in this estimate of effect. LIVER TRANSPLANTATION: HIV+ VS. HIV#ENTITYSTARTX02212; Based on a combined HIV+ cohort sample size of 198 patient across five studies, the risk of death after liver transplantation in an HIV+ cohort (with at least 50% of the cohort co-infected with HCV+) is statistically significantly 64% greater compared with an HIV- cohort (HR: 1.64; 95% CI: 1.32, 2.02). The quality of evidence supporting this outcome is very low. Death censored graft survival was reported for an HIV+ cohort in one study (n=11) however the DCGS rate of the contemporaneous control HIV- cohort was not reported. Because of sparse data the quality of evidence supporting this outcome is very low indicating death censored graft survival is uncertain. Both the CD4+ T-cell count and HIV viral load appear controlled post transplant with an incidence of opportunistic infection of 20.5%. However, the quality of this evidence for these outcomes is very low indicating uncertainty in these effects. Similarly, because of very low quality evidence there is uncertainty in the rate of acute graft rejection among both the HIV+ and HIV- groups LIVER TRANSPLANTATION: HIV+/HCV+ VS. HCV+ Based on a combined HIV+/HCV+ cohort sample size of 156 from seven studies, the risk of death after liver transplantation is significantly greater (2.8 fold) in a co-infected cohort compared with an HCV+ mono-infected cohort (HR: 2.81; 95% CI: 1.47, 5.37). The quality of evidence supporting this outcome is very low. Death censored graft survival evidence was not available. Regarding disease progression, based on a combined sample size of 71 persons in the co-infected cohort, the CD4+ T-cell count and HIV viral load appear controlled post transplant; however, again the quality of evidence supporting this outcome is very low. The rate of opportunistic infection in the co-infected cohort was 7.2%. The quality of evidence supporting this estimate is very low, indicating uncertainty in these estimates of effect. Based on a combined HIV+/HCV+ cohort (n=57) the rate of acute graft rejection does not differ to that of an HCV+ mono-infected cohort (OR: 0.88; 95% CI: 0.44, 1.76). Also based on a combined HIV+/HCV+ cohort (n=83), the rate of HCV+ recurrence does not differ to that of an HCV+ mono-infected cohort (OR: 0.66; 95% CI: 0.27, 1.59). In both cases, the quality of the supporting evidence was very low. Overall, because of very low quality evidence there is uncertainty in the effect of kidney or liver transplantation in HIV+ persons with end stage organ failure compared with those not infected with HIV. Examining the economics of this issue, the cost of kidney and liver transplants in an HIV+ patient population are, on average, 56K and 147K per case, based on both Canadian and American experiences.","ISSN":"1915-7398","note":"PMID: 23074407","shortTitle":"Kidney and liver organ transplantation in persons with human immunodeficiency virus","journalAbbreviation":"Ont Health Technol Assess Ser","language":"eng","author":[{"family":"Health Quality Ontario","given":""}],"issued":{"date-parts":[["2010"]]},"PMID":"23074407"}}],"schema":""} [40]. Further economic analyses to assess cost-effectiveness are needed.SELECTION OF HIV POSITIVE PATIENTS FOR LIVER TRANSPLANTATIONPatients with HIV should meet the generally accepted indications for liver transplant as patients without HIV including advanced liver disease with a MELD of at least 15 or having an indication for an appealed MELD score (i.e., MELD exception points) such as hepatocellular carcinoma, hepatopulmonary syndrome or portopulmonary syndrome ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"dernek1e8","properties":{"formattedCitation":"{\\rtf \\super [51]\\nosupersub{}}","plainCitation":"[51]"},"citationItems":[{"id":531,"uris":[""],"uri":[""],"itemData":{"id":531,"type":"article-journal","title":"Indications for liver transplantation","container-title":"Gastroenterology","page":"1764-1776","volume":"134","issue":"6","source":"NCBI PubMed","abstract":"Patients should be considered for liver transplantation if they have evidence of fulminant hepatic failure, a life-threatening systemic complication of liver disease, or a liver-based metabolic defect or, more commonly, cirrhosis with complications such as hepatic encephalopathy, ascites, hepatocellular carcinoma, hepatorenal syndrome, or bleeding caused by portal hypertension. While the complications of cirrhosis can often be managed relatively effectively, they indicate a change in the natural history of the disease that should lead to consideration of liver transplantation. Referral to a liver transplant center is followed by a detailed medical evaluation to ensure that transplantation is technically feasible, medically appropriate, and in the best interest of both the patient and society. Patients approved for transplantation are placed on a national transplant list, although donor organs are allocated locally and regionally. Since 2002, priority for transplantation has been determined by the Model of End-Stage Liver Disease (MELD) score, which provides donor organs to listed patients with the highest estimated short-term mortality.","DOI":"10.1053/j.gastro.2008.02.028","ISSN":"1528-0012","note":"PMID: 18471553","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"O'Leary","given":"Jacqueline G"},{"family":"Lepe","given":"Rita"},{"family":"Davis","given":"Gary L"}],"issued":{"date-parts":[["2008",5]]},"PMID":"18471553"}}],"schema":""} [51]. They must be able to tolerate the surgery from a cardiovascular and respiratory standpoint and have a satisfactory psychosocial assessment. Patients with a history of substance abuse, including alcohol, must be abstinent and have completed a treatment program. Most programs, including ours, require a minimum of 6 mo of abstinence even though this interval is arbitrary ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2c950efduj","properties":{"formattedCitation":"{\\rtf \\super [52]\\nosupersub{}}","plainCitation":"[52]"},"citationItems":[{"id":307,"uris":[""],"uri":[""],"itemData":{"id":307,"type":"article-journal","title":"Should length of sobriety be a major determinant in liver transplant selection?","container-title":"Current opinion in organ transplantation","page":"259-264","volume":"18","issue":"3","source":"NCBI PubMed","abstract":"PURPOSE OF REVIEW: For patients with alcoholic liver disease, most liver transplant programs enforce a mandatory period of sustained abstinence prior to considering transplant. The '6-month' rule may eliminate potentially acceptable transplant candidates from a lifesaving procedure. This review focuses on the use of sobriety length as a determinant of transplant candidacy and as a predictor of future alcohol use. We will also review the use of liver transplant in patients with severe alcoholic hepatitis, and the impact of alcohol use on posttransplant outcomes.\nRECENT FINDINGS: Patients with alcoholic hepatitis that underwent transplantation had an increased survival when compared with controls. Alcohol relapse after transplantation was infrequent. Similarly, a United Network for Organ Sharing database review revealed similar survival in patients transplanted for alcoholic hepatitis versus alcoholic cirrhosis. Allograft loss due to alcohol use was not seen. However, alcohol usage after transplantation has been associated with a lower long-term survival in both alcoholic and nonalcoholic recipients.\nSUMMARY: The 6-month rule is insufficient in predicting relapse risk. Liver transplantation may be lifesaving in cases of alcoholic hepatitis and inflexible sobriety rules may eliminate patients from transplant consideration at a low risk of relapse. An ongoing alcohol use assessment, both pre- and posttransplant, are critical to achieving good long-term outcomes.","DOI":"10.1097/MOT.0b013e32835fb94b","ISSN":"1531-7013","note":"PMID: 23492643","journalAbbreviation":"Curr Opin Organ Transplant","language":"eng","author":[{"family":"Rice","given":"John P"},{"family":"Lucey","given":"Michael R"}],"issued":{"date-parts":[["2013",6]]},"PMID":"23492643"}}],"schema":""} [52].Patients should be on a stable treatment regimen for their HIV with documented adherence and viral loads being undetectable for at least a 6-mo interval. Preferred antiretroviral agents as part of the HAART regimen include raltegravir, efavirenz, maraviroc and rilpivirine. Zidovudine and protease inhibitors are avoided when possible due to significant anemia and drug interactions respectively. Most nucleoside reverse transcriptase inhibitors can be used. Didanosine and stavudine are the only agents truly contraindicated given the risk of potentially fatal lactic acidosis. Antiretroviral therapy is now recommended in all HIV-infected patients, regardless of CD4 count, assuming they understand the risks and benefits of therapy and are committed to adherence ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1c5lujjfdt","properties":{"formattedCitation":"{\\rtf \\super [53]\\nosupersub{}}","plainCitation":"[53]"},"citationItems":[{"id":378,"uris":[""],"uri":[""],"itemData":{"id":378,"type":"report","title":"Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents","publisher":"Department of Health and Human Services","URL":"","author":[{"family":"Panel on Antiretroviral Guidelines for Adults and Adolescents","given":""}]}}],"schema":""} [53]. In the context of potential transplantation and subsequent immunosuppression as well as the numerous options for therapy currently, we would recommend all patients be on HAART prior to transplant.Current guidelines from the American Society of Transplantation (AST), based on the National Institute of Health studies, suggest that patients with no AIDS defining conditions should have a CD4+ T cell count > 100 cells/L and for patients with AIDS defining disease, a CD4+ T cell count >200 cells/L for at least 3 mo before transplant ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"26h72153do","properties":{"formattedCitation":"{\\rtf \\super [54]\\nosupersub{}}","plainCitation":"[54]"},"citationItems":[{"id":360,"uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Human immunodeficiency virus in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"169-178","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12109","ISSN":"1600-6143","note":"PMID: 23465009","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Blumberg","given":"E A"},{"family":"Rogers","given":"C C"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465009"}}],"schema":""} [54]. In practice, there may be significant variation between centers. In our center, we require a CD4 count ≥ 150 cells/L for at least 6 mo or, if the CD4 count is between 100-150, as is not uncommon in those with portal hypertension and hypersplenism, the CD4% should be ≥ 20% for at least 6 mo. Patients treated with interferon based anti-HCV treatment experience a drop in their absolute CD4 counts ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"13cp157h0b","properties":{"formattedCitation":"{\\rtf \\super [55]\\nosupersub{}}","plainCitation":"[55]"},"citationItems":[{"id":379,"uris":[""],"uri":[""],"itemData":{"id":379,"type":"article-journal","title":"Effect of hepatitis C treatment on CD4+ T-cell counts and the risk of death in HIV-HCV-coinfected patients: the COHERE collaboration","container-title":"Antiviral therapy","page":"1541-1550","volume":"17","issue":"8","source":"NCBI PubMed","abstract":"BACKGROUND: The short- and long-term effects of anti-hepatitis C treatment on mortality in the HIV-HCV-coinfected population have not been evaluated in observational cohorts. Such evaluations must use methods that allow for time-varying prognostic factors that both predict treatment and are affected by prior treatment. We aimed to study immunological changes in HIV-HCV-coinfected individuals during HCV treatment and to estimate the effect of HCV-treatment on mortality.\nMETHODS: Patients were included if they were aged ≥16 years, were HIV-HCV-coinfected and were enrolled in the COHERE cohort. Data were pooled within COHERE in December 2009 in EuroCoord. Random-effects models were used to model immunological changes during HCV treatment. Marginal structural models were used to estimate the effect of HCV treatment on mortality, allowing for time-dependent confounders affected by prior treatment.\nRESULTS: In total, 780/6,433 (12%) HIV-HCV-coinfected patients initiated HCV treatment (interferon [IFN] and ribavirin n=692, IFN alone n=88). CD4(+) T-cell counts decreased during the first 12 weeks of treatment (P<0.0001) and stabilized from week 24 onwards. The estimated mortality hazard ratio for comparing HCV-treated with -untreated individuals was 0.72 (95% CI 0.43, 1.21). The estimated hazard ratio for liver-related death was 0.57 (95% CI 0.21, 1.55).\nCONCLUSIONS: Despite its effect in reducing CD4(+) T-cell counts, the effect of HCV treatment on mortality was in the direction of benefit and our results excluded a substantial increase in mortality. Such benefit may be related to a lower risk of liver-related death. New HCV treatment strategies might contribute to a further reduction in mortality.","DOI":"10.3851/IMP2263","ISSN":"2040-2058","note":"PMID: 22869294","shortTitle":"Effect of hepatitis C treatment on CD4+ T-cell counts and the risk of death in HIV-HCV-coinfected patients","journalAbbreviation":"Antivir. Ther. (Lond.)","language":"eng","author":[{"family":"HCV working group of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord","given":""}],"issued":{"date-parts":[["2012"]]},"PMID":"22869294"}}],"schema":""} [55]. Therefore, to accurately reflect their immune status in the context of transplantation, they should have their CD4 count performed prior to beginning interferon treatment; a reasonable interval would be 4 to 6 mo. We consider a history of multi-drug resistant HIV a relative contraindication to transplantation given the potential challenges of controlling HIV post transplant; however as newer options for therapy continue to be developed, this needs to be reviewed on a case by case basis by the infectious diseases consultant to assess the likelihood of HIV viral breakthrough and the potential for future options.In general, most opportunistic infections (OI) are not absolute contraindications to transplantation; absolute contraindications are listed in Table 3, which are congruent with the AST guidelines ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"25acpc0dvk","properties":{"formattedCitation":"{\\rtf \\super [54]\\nosupersub{}}","plainCitation":"[54]"},"citationItems":[{"id":360,"uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Human immunodeficiency virus in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"169-178","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12109","ISSN":"1600-6143","note":"PMID: 23465009","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Blumberg","given":"E A"},{"family":"Rogers","given":"C C"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465009"}}],"schema":""} [54]. Patients should have been successfully treated for the OI with a reasonable interval of time elapsing following the completion of therapy to allow for immune reconstitution with HAART; we suggest at least 12 mo since the infection. Consultation with an infectious diseases specialist with regards to the risk of recurrence post transplant as well as the need for any additional prophylactic therapies post transplant is also recommended.For the HIV/HCV co-infected patient, simultaneous liver-kidney transplantation is not recommended given poor outcomes ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2h8ma9vtkq","properties":{"formattedCitation":"{\\rtf \\super [2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"716-726","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.","DOI":"10.1002/lt.23411","ISSN":"1527-6473","note":"PMID: 22328294","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Terrault","given":"Norah A"},{"family":"Roland","given":"Michelle E"},{"family":"Schiano","given":"Thomas"},{"family":"Dove","given":"Lorna"},{"family":"Wong","given":"Michael T"},{"family":"Poordad","given":"Fred"},{"family":"Ragni","given":"Margaret V"},{"family":"Barin","given":"Burc"},{"family":"Simon","given":"David"},{"family":"Olthoff","given":"Kim M"},{"family":"Johnson","given":"Lynt"},{"family":"Stosor","given":"Valentina"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Fung","given":"John"},{"family":"Sherman","given":"Kenneth E"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Slakey","given":"Douglas"},{"family":"Berg","given":"Carl L"},{"family":"Carlson","given":"Laurie"},{"family":"Ferrell","given":"Linda"},{"family":"Stablein","given":"Donald M"},{"family":"Odim","given":"Jonah"},{"family":"Fox","given":"Lawrence"},{"family":"Stock","given":"Peter G"},{"family":"Solid Organ Transplantation in HIV: Multi-Site Study Investigators","given":""}],"issued":{"date-parts":[["2012",6]]},"PMID":"22328294"}}],"schema":""} [2] as compared to the mono-infected HCV patient ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"27gopq6d5p","properties":{"formattedCitation":"{\\rtf \\super [56]\\nosupersub{}}","plainCitation":"[56]"},"citationItems":[{"id":424,"uris":[""],"uri":[""],"itemData":{"id":424,"type":"article-journal","title":"Outcome of combined liver and kidney transplantation in hepatitis C: a single-center long-term follow-up experience","container-title":"Transplantation proceedings","page":"1713-1716","volume":"41","issue":"5","source":"NCBI PubMed","abstract":"INTRODUCTION: Hepatitis C (HCV) cirrhosis is the prevalent liver disease requiring liver transplantation in the United States. Candidates who also have end-stage renal disease, chronic renal disease stage 4, or prolonged hepatorenal syndrome are considered for combined liver and kidney transplantation (CLKT).\nMATERIALS AND METHODS: We performed a retrospective study of HCV(+) and HCV(-) CLKT patients with more than 12 months of follow-up and HCV(+) patients with isolated liver transplant (OLT) to compare the outcomes of various groups.\nRESULTS: Since 1988, 2983 OLTs were performed at our institution including 58 CLKTs. Of these, 23 were HCV(+) subjects who were significantly older than HCV(-) CLKT patients. Race, pretransplant dialysis time, renal indication for CLKT, Model for End-stage Liver Disease score, donor age, liver and kidney rejection as well as occurrence of posttransplant hypertension were similar among HCV(+) and HCV(-) CLKT patients. Posttransplant diabetes was observed in 80% of the HCV(+) group and 30% of the HCV(-) group (P = .01). Renal function seemed to be better in HCV(-) when compared with HCV(+) subjects at 5 years (P = .09). Overall patient survival for HCV(+) CLKT, HCV(-) CLKT, and HCV(+) OLT groups at 1, 2, and 5 years were not significantly different (P = .6).\nCONCLUSION: HCV positivity should not exclude appropriate candidates for CLKT.","DOI":"10.1016/j.transproceed.2009.02.103","ISSN":"1873-2623","note":"PMID: 19545713","shortTitle":"Outcome of combined liver and kidney transplantation in hepatitis C","journalAbbreviation":"Transplant. Proc.","language":"eng","author":[{"family":"del Pozo","given":"A C"},{"family":"Martín","given":"J D R"},{"family":"Rodriguez-Laiz","given":"G"},{"family":"Sturdevant","given":"M"},{"family":"Iyer","given":"K"},{"family":"Schwartz","given":"M"},{"family":"Schiano","given":"T"},{"family":"Lerner","given":"S"},{"family":"Ames","given":"S"},{"family":"Bromberg","given":"J"},{"family":"Thung","given":"S"},{"family":"de Boccardo","given":"G"}],"issued":{"date-parts":[["2009",6]]},"PMID":"19545713"}}],"schema":""} [56]. Similarly, HCV positive grafts should be avoided in HIV co-infected patients given inferior survival ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"3muih6vdi","properties":{"formattedCitation":"{\\rtf \\super [2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"716-726","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.","DOI":"10.1002/lt.23411","ISSN":"1527-6473","note":"PMID: 22328294","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Terrault","given":"Norah A"},{"family":"Roland","given":"Michelle E"},{"family":"Schiano","given":"Thomas"},{"family":"Dove","given":"Lorna"},{"family":"Wong","given":"Michael T"},{"family":"Poordad","given":"Fred"},{"family":"Ragni","given":"Margaret V"},{"family":"Barin","given":"Burc"},{"family":"Simon","given":"David"},{"family":"Olthoff","given":"Kim M"},{"family":"Johnson","given":"Lynt"},{"family":"Stosor","given":"Valentina"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Fung","given":"John"},{"family":"Sherman","given":"Kenneth E"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Slakey","given":"Douglas"},{"family":"Berg","given":"Carl L"},{"family":"Carlson","given":"Laurie"},{"family":"Ferrell","given":"Linda"},{"family":"Stablein","given":"Donald M"},{"family":"Odim","given":"Jonah"},{"family":"Fox","given":"Lawrence"},{"family":"Stock","given":"Peter G"},{"family":"Solid Organ Transplantation in HIV: Multi-Site Study Investigators","given":""}],"issued":{"date-parts":[["2012",6]]},"PMID":"22328294"}}],"schema":""} [2]. Patients should ideally have a BMI > 21 kg/m2; in otherwise acceptable candidates with BMIs < 21 kg/m2, nutritional supplementation and reassessment once the BMI exceeds 21 is reasonable; this is in keeping with the 2013 AST guidelines ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"27po2ogq25","properties":{"formattedCitation":"{\\rtf \\super [54]\\nosupersub{}}","plainCitation":"[54]"},"citationItems":[{"id":360,"uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Human immunodeficiency virus in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"169-178","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12109","ISSN":"1600-6143","note":"PMID: 23465009","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Blumberg","given":"E A"},{"family":"Rogers","given":"C C"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465009"}}],"schema":""} [54]. We would suggest that patients with natural MELD scores > 25 be reviewed on a case by case given the worse outcomes seen in this population. Additionally, it is recognized that co-infected patients have more rapid deterioration of liver disease and a higher risk of death on the list than mono-infected patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"4S7nJyjZ","properties":{"formattedCitation":"{\\rtf \\super [1,57]\\nosupersub{}}","plainCitation":"[1,57]"},"citationItems":[{"id":426,"uris":[""],"uri":[""],"itemData":{"id":426,"type":"article-journal","title":"The model for end-stage liver disease score is the best prognostic factor in human immunodeficiency virus 1-infected patients with end-stage liver disease: a prospective cohort study","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"1133-1141","volume":"15","issue":"9","source":"NCBI PubMed","abstract":"End-stage liver disease (ESLD) has become the main cause of mortality in patients coinfected by human immunodeficiency virus (HIV) and hepatitis B virus or hepatitis C virus in developed countries. The aim of this study was to describe the natural history of and prognostic factors for ESLD, with particular attention paid to features affecting liver transplantation. This was a prospective cohort study in 2 Spanish community-based hospitals performed between 1999 and 2004. One hundred four consecutive patients with cirrhosis and a first clinical decompensation of their chronic liver disease or hepatocellular carcinoma were included in the study. During a median follow-up of 10 months (endpoint: death, liver transplantation, or the last checkup date), 61 patients (59%) died. The probability of mortality (Kaplan-Meier method) at 1, 2, and 3 years was 43% [95% confidence interval (CI), 34%-60%], 59% (95% CI, 48%-70%), and 70% (95% Cl, 59%-81%), respectively. In a multivariate analysis, the Model for End-Stage Liver Disease (MELD) score and the inability to reach an undetectable plasma HIV-1 RNA viral load at any time during follow-up were the only variables independently associated with the risk of death (P < 0.001). Fifteen (14%) of the 104 patients were accepted for liver transplantation, although only 5 underwent the procedure, and 10 died while on the waiting list. The waiting list mortality rate in patients with a MELD score < 20 and in patients with a MELD score >20 was 58% and 100%, respectively (median follow-up, 5 months). In conclusion, HIV-1-infected patients with ESLD, especially those with poorly controlled HIV and a high MELD score, have a poor short-term outcome. The MELD score may be useful in deciding whether to indicate liver transplantation in these patients. However, because only a small proportion of the patients in this study were considered candidates for liver transplantation and most died while on the waiting list, few received a transplant.","DOI":"10.1002/lt.21735","ISSN":"1527-6473","note":"PMID: 19718643","shortTitle":"The model for end-stage liver disease score is the best prognostic factor in human immunodeficiency virus 1-infected patients with end-stage liver disease","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Murillas","given":"Javier"},{"family":"Rimola","given":"Antonio"},{"family":"Laguno","given":"Montserrat"},{"family":"de Lazzari","given":"Elisa"},{"family":"Rascón","given":"Javier"},{"family":"Agüero","given":"Fernando"},{"family":"Blanco","given":"José L"},{"family":"Moitinho","given":"Eduardo"},{"family":"Moreno","given":"Asunción"},{"family":"Miró","given":"José M"},{"family":"ESLD-HIV Working Group Investigators","given":""}],"issued":{"date-parts":[["2009",9]]},"PMID":"19718643"}},{"id":11,"uris":[""],"uri":[""],"itemData":{"id":11,"type":"article-journal","title":"OPTN/SRTR 2011 Annual Data Report: liver","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"73-102","volume":"13 Suppl 1","source":"NCBI PubMed","abstract":"The current liver allocation system, introduced in 2002, decreased the importance of waiting time for allocation priorities; the number of active wait-listed candidates and median waiting times were immediately reduced. However, the total number of adult wait-listed candidates has increased since 2002, and median waiting time has increased since 2006. Pretransplant mortality rates have been stable, but the number of candidates withdrawn from the list as being too sick to undergo transplant nearly doubled between 2009 and 2011. Deceased donation rates have remained stable, with an increasing proportion of expanded criteria donors. Living donation has decreased over the past 10 years. Transplant outcomes remain robust, with continuously improving graft survival rates for deceased donor, living donor, and donation after circulatory death livers. Numbers of new and prevalent pediatric candidates on the waiting list have decreased. Pediatric pretransplant mortality has decreased, most dramatically for candidates aged less than 1 year. The transplant rate has increased since 2002, and is highest in candidates aged less than 1 year. Graft survival continues to improve for pediatric recipients of deceased donor and living donor livers. Incidence of acute rejections increases with time after transplant. Posttransplant lymphoproliferative disorder remains an important concern in pediatric recipients.","DOI":"10.1111/ajt.12021","ISSN":"1600-6143","note":"PMID: 23237697","shortTitle":"OPTN/SRTR 2011 Annual Data Report","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Kim","given":"W R"},{"family":"Stock","given":"P G"},{"family":"Smith","given":"J M"},{"family":"Heimbach","given":"J K"},{"family":"Skeans","given":"M A"},{"family":"Edwards","given":"E B"},{"family":"Harper","given":"A M"},{"family":"Snyder","given":"J J"},{"family":"Israni","given":"A K"},{"family":"Kasiske","given":"B L"}],"issued":{"date-parts":[["2013",1]]},"PMID":"23237697"}}],"schema":""} [1,57], thus a detailed discussion of potential benefit of live donor liver transplantation should occur. At this time, we do not recommend re-transplantation of patients with HIV/HCV co-infection outside of study protocols given the poor 42% 3 year survival seen in a small series of 14 patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"16204574pc","properties":{"formattedCitation":"{\\rtf \\super [58]\\nosupersub{}}","plainCitation":"[58]"},"citationItems":[{"id":472,"uris":[""],"uri":[""],"itemData":{"id":472,"type":"article-journal","title":"Liver retransplantation in HIV-infected patients: a prospective cohort study","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"2465-2476","volume":"12","issue":"9","source":"NCBI PubMed","abstract":"Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.","DOI":"10.1111/j.1600-6143.2012.04142.x","ISSN":"1600-6143","note":"PMID: 22703615","shortTitle":"Liver retransplantation in HIV-infected patients","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Gastaca","given":"M"},{"family":"Aguero","given":"F"},{"family":"Rimola","given":"A"},{"family":"Montejo","given":"M"},{"family":"Miralles","given":"P"},{"family":"Lozano","given":"R"},{"family":"Castells","given":"L"},{"family":"Abradelo","given":"M"},{"family":"Mata","given":"M de la"},{"family":"San Juan Rodríguez","given":"F"},{"family":"Cordero","given":"E"},{"family":"Campo","given":"S del"},{"family":"Manzardo","given":"C"},{"family":"de Urbina","given":"J O"},{"family":"Pérez","given":"I"},{"family":"Rosa","given":"G de la"},{"family":"Miro","given":"J M"},{"family":"FIPSE OLT-HIV investigators","given":""}],"issued":{"date-parts":[["2012",9]]},"PMID":"22703615"}}],"schema":""} [58].SUMMARY OF RECOMMENDATIONS FOR THE PRE-TRANSPLANT MANAGEMENT OF THE PATIENT WITH HIV AND VIRAL HEPATITIS CO-INFECTIONIn co-infected HCV patients, successful treatment of HCV will likely offer significant improvement in transplant outcomes given the adverse effects of recurrent HCV in the co-infected ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"83l8vd619","properties":{"formattedCitation":"{\\rtf \\super [44]\\nosupersub{}}","plainCitation":"[44]"},"citationItems":[{"id":319,"uris":[""],"uri":[""],"itemData":{"id":319,"type":"article-journal","title":"Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"2983-2993","volume":"6","issue":"12","source":"NCBI PubMed","abstract":"Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.","DOI":"10.1111/j.1600-6143.2006.01546.x","ISSN":"1600-6135","note":"PMID: 17062005","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"de Vera","given":"M E"},{"family":"Dvorchik","given":"I"},{"family":"Tom","given":"K"},{"family":"Eghtesad","given":"B"},{"family":"Thai","given":"N"},{"family":"Shakil","given":"O"},{"family":"Marcos","given":"A"},{"family":"Demetris","given":"A"},{"family":"Jain","given":"A"},{"family":"Fung","given":"J J"},{"family":"Ragni","given":"M V"}],"issued":{"date-parts":[["2006",12]]},"PMID":"17062005"}}],"schema":""} [44] and mono-infected HCV populations ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"idd02fsai","properties":{"formattedCitation":"{\\rtf \\super [59]\\nosupersub{}}","plainCitation":"[59]"},"citationItems":[{"id":428,"uris":[""],"uri":[""],"itemData":{"id":428,"type":"article-journal","title":"Management of the transplant recipient with chronic hepatitis C","container-title":"Clinics in liver disease","page":"73-91","volume":"17","issue":"1","source":"NCBI PubMed","abstract":"More than one-third of listed potential liver recipients in the US are infected with the hepatitis C virus (HCV). Recurrence of infection with HCV after liver transplantation is associated with accelerated graft loss and diminished patient survival. Current HCV treatments using peginterferon and ribavirin either alone or with first generation protease inhibitors (telaprevir, boceprevir) are limited by suboptimal viral response, drug-drug interaction, and side effects, some of which may be graft- or life-threatening. Rapid advances in new drug therapy for HCV promise to improve outcomes, reduce side effects and drug-drug interaction, shorten treatment duration, and simplify treatment regimens.","DOI":"10.1016/j.cld.2012.09.013","ISSN":"1557-8224","note":"PMID: 23177284","journalAbbreviation":"Clin Liver Dis","language":"eng","author":[{"family":"Burton","given":"James R, Jr"},{"family":"Everson","given":"Gregory T"}],"issued":{"date-parts":[["2013",2]]},"PMID":"23177284"}}],"schema":""} [59] as well as increased mortality on the waitlist ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"v9p3712kl","properties":{"formattedCitation":"{\\rtf \\super [60]\\nosupersub{}}","plainCitation":"[60]"},"citationItems":[{"id":458,"uris":[""],"uri":[""],"itemData":{"id":458,"type":"article-journal","title":"Pretransplant survival is shorter in HIV-positive than HIV-negative subjects with end-stage liver disease","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"1425-1430","volume":"11","issue":"11","source":"NCBI PubMed","abstract":"Despite improved survival after liver transplantation (OLTX) in HIV-positive individuals treated with highly active antiretroviral therapy (HAART), some transplant candidates do not survive to OLTX. To determine if pretransplant outcome is related to severity of liver disease and/or HIV infection, we prospectively evaluated 58 consecutive HIV-positive candidates seen at a single center from 1997-2002. Of the 58, 15 (25.9%) were transplanted, whereas 21 (36.2%) died before OLTX, a median one month of evaluation, with more than half of those (12 of 21, 57.1%) dying from infection. By contrast, of 1,359 HIV-negative candidates, 860 (63.3%) were transplanted, whereas 211 (15.5%) died before OLTX (P < 0.001). The cumulative survival following initial evaluation was significantly shorter among HIV-positive than HIV-negative candidates (880 vs. 1,427 days, P = 0.035, Breslow) but was not related to the initial pretransplant MELD score (16 vs. 15), INR (1.5 vs. 1.5), creatinine (1.3 vs. 1.3 mg/dL), or total bilirubin (6.6 vs. 5.7 mg/dL), respectively, all P > 0.05. Among untransplanted HIV-positive candidates, the 21 who died did not differ from the 22 surviving in initial MELD (15 vs. 13), CD4 (230 vs. 327/microL), HIV load (both < 400 copies/mL), HAART intolerance (10/21, 47.6% vs. 10/22, 45.4%), or HCV infection (16/21, 76.2% vs. 16/22, 72.3%), all P > 0.05. Further, the 21 did not differ from the 15 transplanted in pre-OLTX CD4, HIV load, or MELD score, all P > 0.05. In conclusion, pretransplant survival appears shorter in HIV-positive OLTX candidates and is unrelated to severity of liver or HIV disease. Further study is warranted to determine risk factors for poorer pretransplant outcomes.","DOI":"10.1002/lt.20534","ISSN":"1527-6465","note":"PMID: 16237709","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Ragni","given":"Margaret V"},{"family":"Eghtesad","given":"Bijan"},{"family":"Schlesinger","given":"Kimberly W"},{"family":"Dvorchik","given":"Igor"},{"family":"Fung","given":"John J"}],"issued":{"date-parts":[["2005",11]]},"PMID":"16237709"}}],"schema":""} [60]. However, treatment can be challenging due to the interaction of novel directly acting anti-HCV agents (i.e., viral protease and polymerase inhibitors) with HAART ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"febjbdml4","properties":{"formattedCitation":"{\\rtf \\super [33]\\nosupersub{}}","plainCitation":"[33]"},"citationItems":[{"id":406,"uris":[""],"uri":[""],"itemData":{"id":406,"type":"article-journal","title":"Focus on drug interactions: the challenge of treating hepatitis C virus infection with direct-acting antiviral drugs in the HIV-positive patient","container-title":"Current opinion in infectious diseases","page":"50-57","volume":"26","issue":"1","source":"NCBI PubMed","abstract":"PURPOSE OF REVIEW: Successful treatment of hepatitis C virus (HCV) infection is necessary for the survival of HIV-infected patients. This review covers the outcomes of current therapy, first-generation HCV direct-acting antivirals (DAAs) and their drug-to-drug interactions (DDIs). Understanding DDIs between HIV antiretroviral therapy (ART) and the DAAs in development is important to assure the best management of the HIV/HCV coinfected individuals.\nRECENT FINDINGS: The two first-in-class DAAs were approved for clinical use in 2011. The first trials with boceprevir or telaprevir added to standard therapy in HIV/HCV coinfected patients revealed triple therapy to be efficacious with significantly improved sustained virological response rates. However, these DAAs were associated with more and worse adverse effects, as well as with significant DDIs with multiple drugs, including ART. Early data on DAAs in development suggest improved efficacy and safety and the potential for lesser DDIs.\nSUMMARY: Anti-HCV therapy is fundamental in coinfected patients, but the approved therapies are suboptimal. The first-generation of approved HCV DAAs improved efficacy of therapy in coinfected patients, but have multiple safety concerns, including potentially serious drug interactions with ART. Early results from newer DAAs are promising.","DOI":"10.1097/QCO.0b013e32835c2027","ISSN":"1473-6527","note":"PMID: 23242341","shortTitle":"Focus on drug interactions","journalAbbreviation":"Curr. Opin. Infect. Dis.","language":"eng","author":[{"family":"Rodríguez-Torres","given":"Maribel"}],"issued":{"date-parts":[["2013",2]]},"PMID":"23242341"}}],"schema":""} [33] especially in the context of advanced liver disease and risk of decompensation. If treatment is not feasible, complications of liver disease should be managed similar to the non-HIV infected population.For patients with HIV-HBV co-infection, the ideal antiretroviral regimen should contain tenofovir, with appropriate dose adjustment for renal function. If tenofovir is poorly tolerated, entecavir is suggested in conjunction with a fully suppressive HIV treatment regimen. If patients have any history of lamivudine exposure, given high rates of lamivudine resistant HBV in the co-infected population, it is recommended that if entecavir is used, it be at a 1 mg dose daily. Both HBV/HIV and HCV/HIV co-infected patients with HCC seem to have a higher risk of tumor progression outside of most transplant centers’ criteria including the current UNOS standard of the Milan criteria ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"12m62o2uhd","properties":{"formattedCitation":"{\\rtf \\super [61]\\nosupersub{}}","plainCitation":"[61]"},"citationItems":[{"id":416,"uris":[""],"uri":[""],"itemData":{"id":416,"type":"article-journal","title":"Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis","container-title":"The New England journal of medicine","page":"693-699","volume":"334","issue":"11","source":"NCBI PubMed","abstract":"BACKGROUND: The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult.\nMETHODS: We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Thirty-three patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation, the patients were followed prospectively for a median of 26 months (range, 9 to 54). No anticancer treatment was given after transplantation.\nRESULTS: The overall mortality rate was 17 percent. After four years, the actuarial survival rate was 75 percent and the rate of recurrence-free survival was 83 percent. Hepatocellular carcinoma recurred in four patients (8 percent). The overall and recurrence-free survival rates at four years among the 35 patients (73 percent of the total) who met the predetermined criteria for the selection of small hepatocellular carcinomas at pathological review of small hepatocellular carcinomas at pathological review of the explanted liver wer 85 percent and 92 percent, respectively, whereas the rates in the 13 patients (27 percent) whose tumors exceeded these limits were 50 percent and 59 percent, respectively (P=0.01 for overall survival; P=0.002 for recurrence-free survival). In this group of 48 patients with early-stage tumors, tumor-node-metastasis status, the number of tumors, the serum alphafetoprotein concentration, treatment received before transplantation, and 10 other variables were not significantly correlated with survival.\nCONCLUSIONS: Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.","DOI":"10.1056/NEJM199603143341104","ISSN":"0028-4793","note":"PMID: 8594428","journalAbbreviation":"N. Engl. J. Med.","language":"eng","author":[{"family":"Mazzaferro","given":"V"},{"family":"Regalia","given":"E"},{"family":"Doci","given":"R"},{"family":"Andreola","given":"S"},{"family":"Pulvirenti","given":"A"},{"family":"Bozzetti","given":"F"},{"family":"Montalto","given":"F"},{"family":"Ammatuna","given":"M"},{"family":"Morabito","given":"A"},{"family":"Gennari","given":"L"}],"issued":{"date-parts":[["1996",3,14]]},"PMID":"8594428"}}],"schema":""} [61], and total tumor volume ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1vrnjunenh","properties":{"formattedCitation":"{\\rtf \\super [62]\\nosupersub{}}","plainCitation":"[62]"},"citationItems":[{"id":418,"uris":[""],"uri":[""],"itemData":{"id":418,"type":"article-journal","title":"Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"1107-1115","volume":"14","issue":"8","source":"NCBI PubMed","abstract":"Criteria for the selection of candidates for liver transplantation in the presence of hepatocellular carcinoma (HCC) should accurately predict posttransplant recurrence while not excluding excessive numbers of patients from candidacy. Existing criteria are challenged by the limited accuracy of radiological assessment. The total tumor volume (TTV) was calculated by the addition of the volume of each individual tumor. A preliminary analysis was carried out on HCC patient data from the Alberta Liver Transplant Program (52 patients) and then validated on the populations of the Universities of Toronto and Colorado programs (154 and 82 patients). A TTV cutoff of 115 cm(3) was chosen on the basis of the risk of recurrence with use of a receiver operating characteristic curve. Radiology correlated more closely to pathology with TTV than with Milan and University of California at San Francisco (UCSF) criteria (91% versus 69% and 75% of patients, P < 0.0001). Although more patients met qualifying criteria for transplant with TTV (28%-53% more than Milan and 16%-26% more than UCSF), no deterioration of outcome was demonstrated in an analysis of patients within TTV < or = 115 cm(3) in comparison with those meeting Milan or UCSF classifications at all institutions. Patients with TTV > 115 cm(3) experienced more recurrences and lower patient survival in the Alberta and Colorado series (P < 0.05). When TTV with a cutoff of 115 cm(3) is used for candidate selection, the accuracy of pretransplant radiological assessment is enhanced, with posttransplant outcomes not different from those achieved with Milan and UCSF classifications despite a more inclusive patient population.","DOI":"10.1002/lt.21484","ISSN":"1527-6473","note":"PMID: 18668667","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Toso","given":"Christian"},{"family":"Trotter","given":"James"},{"family":"Wei","given":"Alice"},{"family":"Bigam","given":"David L"},{"family":"Shah","given":"Shimul"},{"family":"Lancaster","given":"Joshua"},{"family":"Grant","given":"David R"},{"family":"Greig","given":"Paul D"},{"family":"Shapiro","given":"A M James"},{"family":"Kneteman","given":"Norman M"}],"issued":{"date-parts":[["2008",8]]},"PMID":"18668667"}}],"schema":""} [62]. Given this, we would obtain imaging every 3 mo to monitor tumor development. As well, given that an AFP rise of > 15 μg/L per month is associated with a poor prognosis in this population ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1he59o4k84","properties":{"formattedCitation":"{\\rtf \\super [63]\\nosupersub{}}","plainCitation":"[63]"},"citationItems":[{"id":414,"uris":[""],"uri":[""],"itemData":{"id":414,"type":"article-journal","title":"Liver transplantation for hepatocellular carcinoma: the impact of human immunodeficiency virus infection","container-title":"Hepatology (Baltimore, Md.)","page":"475-482","volume":"53","issue":"2","source":"NCBI PubMed","abstract":"Liver transplantation (LT) has become an accepted therapy for end-stage liver disease in human immunodeficiency virus-positive (HIV+) patients, but the specific results of LT for hepatocellular carcinoma (HCC) are unknown. Between 2003 and 2008, 21 HIV+ patients and 65 HIV- patients with HCC were listed for LT at a single institution. Patient characteristics and pathological features were analyzed. Univariate analysis for overall survival (OS) and recurrence-free survival (RFS) after LT was applied to identify the impact of HIV infection. HIV+ patients were younger than HIV- patients [median age: 48 (range = 41-63 years) versus 57 years (range = 37-72 years), P < 0.001] and had a higher alpha-fetoprotein (AFP) level [median AFP level: 16 (range = 3-7154 μg/L] versus 13 μg/L (range = 1-552 μg/L), P = 0.04]. There was a trend toward a higher dropout rate among HIV+ patients (5/21, 23%) versus HIV- patients (7/65, 10%, P = 0.08). Sixteen HIV+ patients and 58 HIV- patients underwent transplantation after median waiting times of 3.5 (range = 0.5-26 months) and 2.0 months (range = 0.5-24 months, P = 0.18), respectively. No significant difference was observed in the pathological features of HCC. With median follow-up times of 27 (range = 5-74 months) and 36 months (range = 3-82 months, P = 0.40), OS after LT at 1 and 3 years reached 81% and 74% in HIV+ patients and 93% and 85% in HIV- patients, respectively (P = 0.08). RFS rates at 1 and 3 years were 69% and 69% in HIV+ patients and 89% and 84% in HIV- patients, respectively (P = 0.09). In univariate analysis, HIV status did not emerge as a prognostic factor for OS or RFS.\nCONCLUSION: Because of a higher dropout rate among HIV+ patients, HIV infection impaired the results of LT for HCC on an intent-to-treat basis but had no significant impact on OS and RFS after LT.","DOI":"10.1002/hep.24062","ISSN":"1527-3350","note":"PMID: 21274869","shortTitle":"Liver transplantation for hepatocellular carcinoma","journalAbbreviation":"Hepatology","language":"eng","author":[{"family":"Vibert","given":"Eric"},{"family":"Duclos-Vallée","given":"Jean-Charles"},{"family":"Ghigna","given":"Maria-Rosa"},{"family":"Hoti","given":"Emir"},{"family":"Salloum","given":"Chady"},{"family":"Guettier","given":"Catherine"},{"family":"Castaing","given":"Denis"},{"family":"Samuel","given":"Didier"},{"family":"Adam","given":"René"}],"issued":{"date-parts":[["2011",2]]},"PMID":"21274869"}}],"schema":""} [63], it is suggested that AFP be done monthly as a marker of tumor progression.SUMMARY OF RECOMMENDATIONS FOR THE POST TRANSPLANT MANAGEMENT OF THE HIV/VIRAL HEPATITIS CO-INFECTED PATIENTImmunosuppressionOverall, immunosuppression in the HIV co-infected population is similar in principle to that of the mono-infected patient. The use of an induction agent is controversial; however, given high rejection rates seen ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"h63komcmc","properties":{"formattedCitation":"{\\rtf \\super [2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"716-726","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.","DOI":"10.1002/lt.23411","ISSN":"1527-6473","note":"PMID: 22328294","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Terrault","given":"Norah A"},{"family":"Roland","given":"Michelle E"},{"family":"Schiano","given":"Thomas"},{"family":"Dove","given":"Lorna"},{"family":"Wong","given":"Michael T"},{"family":"Poordad","given":"Fred"},{"family":"Ragni","given":"Margaret V"},{"family":"Barin","given":"Burc"},{"family":"Simon","given":"David"},{"family":"Olthoff","given":"Kim M"},{"family":"Johnson","given":"Lynt"},{"family":"Stosor","given":"Valentina"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Fung","given":"John"},{"family":"Sherman","given":"Kenneth E"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Slakey","given":"Douglas"},{"family":"Berg","given":"Carl L"},{"family":"Carlson","given":"Laurie"},{"family":"Ferrell","given":"Linda"},{"family":"Stablein","given":"Donald M"},{"family":"Odim","given":"Jonah"},{"family":"Fox","given":"Lawrence"},{"family":"Stock","given":"Peter G"},{"family":"Solid Organ Transplantation in HIV: Multi-Site Study Investigators","given":""}],"issued":{"date-parts":[["2012",6]]},"PMID":"22328294"}}],"schema":""} [2], we feel that the use of the interleukin 2 inhibitor basiliximab as a steroid sparing agent is reasonable. Thymoglobulin would not be recommended given the high rate of graft loss seen in the HIV renal transplant group due to increased HCV replication ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"suMr5Bm3","properties":{"formattedCitation":"{\\rtf \\super [64]\\nosupersub{}}","plainCitation":"[64]"},"citationItems":[{"id":430,"uris":[""],"uri":[""],"itemData":{"id":430,"type":"article-journal","title":"Outcomes of kidney transplantation in HIV-infected recipients","container-title":"The New England journal of medicine","page":"2004-2014","volume":"363","issue":"21","source":"NCBI PubMed","abstract":"BACKGROUND: The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.\nMETHODS: We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy.\nRESULTS: Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications.\nCONCLUSIONS: In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; number, NCT00074386.).","DOI":"10.1056/NEJMoa1001197","ISSN":"1533-4406","note":"PMID: 21083386","journalAbbreviation":"N. Engl. J. Med.","language":"eng","author":[{"family":"Stock","given":"Peter G"},{"family":"Barin","given":"Burc"},{"family":"Murphy","given":"Barbara"},{"family":"Hanto","given":"Douglas"},{"family":"Diego","given":"Jorge M"},{"family":"Light","given":"Jimmy"},{"family":"Davis","given":"Charles"},{"family":"Blumberg","given":"Emily"},{"family":"Simon","given":"David"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Lyon","given":"G Marshall"},{"family":"Brayman","given":"Kenneth"},{"family":"Slakey","given":"Doug"},{"family":"Shapiro","given":"Ron"},{"family":"Melancon","given":"Joseph"},{"family":"Jacobson","given":"Jeffrey M"},{"family":"Stosor","given":"Valentina"},{"family":"Olson","given":"Jean L"},{"family":"Stablein","given":"Donald M"},{"family":"Roland","given":"Michelle E"}],"issued":{"date-parts":[["2010",11,18]]},"PMID":"21083386"}}],"schema":""} [64]. The maintenance immunosuppression regimen in HIV-positive recipients is not well defined, and even less is known in HCV/HIV in co-infected patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"h0sihg4uq","properties":{"formattedCitation":"{\\rtf \\super [54]\\nosupersub{}}","plainCitation":"[54]"},"citationItems":[{"id":360,"uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Human immunodeficiency virus in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"169-178","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12109","ISSN":"1600-6143","note":"PMID: 23465009","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Blumberg","given":"E A"},{"family":"Rogers","given":"C C"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465009"}}],"schema":""} [54]. Most programs have used calcineurin inhibitors as the backbone of the maintenance protocol with cyclosporine potentially having some in vivo suppression of HIV ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1oeal1iqq2","properties":{"formattedCitation":"{\\rtf \\super [65]\\nosupersub{}}","plainCitation":"[65]"},"citationItems":[{"id":432,"uris":[""],"uri":[""],"itemData":{"id":432,"type":"article-journal","title":"Cyclosporine blocks incorporation of HIV-1 envelope glycoprotein into virions","container-title":"Journal of virology","page":"4851-4855","volume":"84","issue":"9","source":"NCBI PubMed","abstract":"Cyclosporine (CsA) decreases HIV-1 infectivity by blocking HIV-1 capsid (CA) interaction with target cell cyclophilin A (CypA). Yet, HIV-1 virions produced in the presence of CsA also exhibit decreased infectivity that was previously shown to be independent of the well-characterized HIV-1 CA-CypA interaction. Here, we demonstrate that CsA decreases gp120 and gp41 incorporation into HIV-1 virions and that the fusion of these virions with susceptible target cells is impaired. This effect was not observed with HIV-1 virions pseudotyped with the vesicular stomatitis virus glycoprotein or with the amphotropic envelope protein of murine leukemia virus. It was independent of calcineurin signaling, the endoplasmic reticulum luminal protein cyclophilin B, and the long cytoplasmic tail of gp41. Thus, cyclosporine blocks HIV-1 infectivity via two independent mechanisms, the first involving HIV-1 CA in target cells and the second involving HIV-1 Env in producer cells.","DOI":"10.1128/JVI.01699-09","ISSN":"1098-5514","note":"PMID: 20181694","journalAbbreviation":"J. Virol.","language":"eng","author":[{"family":"Sokolskaja","given":"Elena"},{"family":"Olivari","given":"Silvia"},{"family":"Zufferey","given":"Madeleine"},{"family":"Strambio-De-Castillia","given":"Caterina"},{"family":"Pizzato","given":"Massimo"},{"family":"Luban","given":"Jeremy"}],"issued":{"date-parts":[["2010",5]]},"PMID":"20181694"}}],"schema":""} [65] although cyclosporine may put patients at higher risk of rejection as compared to tacrolimus ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"9im6rgb29","properties":{"formattedCitation":"{\\rtf \\super [64]\\nosupersub{}}","plainCitation":"[64]"},"citationItems":[{"id":430,"uris":[""],"uri":[""],"itemData":{"id":430,"type":"article-journal","title":"Outcomes of kidney transplantation in HIV-infected recipients","container-title":"The New England journal of medicine","page":"2004-2014","volume":"363","issue":"21","source":"NCBI PubMed","abstract":"BACKGROUND: The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.\nMETHODS: We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy.\nRESULTS: Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications.\nCONCLUSIONS: In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; number, NCT00074386.).","DOI":"10.1056/NEJMoa1001197","ISSN":"1533-4406","note":"PMID: 21083386","journalAbbreviation":"N. Engl. J. Med.","language":"eng","author":[{"family":"Stock","given":"Peter G"},{"family":"Barin","given":"Burc"},{"family":"Murphy","given":"Barbara"},{"family":"Hanto","given":"Douglas"},{"family":"Diego","given":"Jorge M"},{"family":"Light","given":"Jimmy"},{"family":"Davis","given":"Charles"},{"family":"Blumberg","given":"Emily"},{"family":"Simon","given":"David"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Lyon","given":"G Marshall"},{"family":"Brayman","given":"Kenneth"},{"family":"Slakey","given":"Doug"},{"family":"Shapiro","given":"Ron"},{"family":"Melancon","given":"Joseph"},{"family":"Jacobson","given":"Jeffrey M"},{"family":"Stosor","given":"Valentina"},{"family":"Olson","given":"Jean L"},{"family":"Stablein","given":"Donald M"},{"family":"Roland","given":"Michelle E"}],"issued":{"date-parts":[["2010",11,18]]},"PMID":"21083386"}}],"schema":""} [64] and may lead to poorer outcomes in the HCV population ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2q2f96ad8q","properties":{"formattedCitation":"{\\rtf \\super [66]\\nosupersub{}}","plainCitation":"[66]"},"citationItems":[{"id":456,"uris":[""],"uri":[""],"itemData":{"id":456,"type":"article-journal","title":"Cyclosporine versus tacrolimus treated liver transplant recipients with chronic hepatitis C: outcomes analysis of the UNOS/OPTN database","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1676-1685","volume":"11","issue":"8","source":"NCBI PubMed","abstract":"Recurrent hepatitis C virus (HCV) remains a problematic cause of morbidity and mortality for liver transplant patients. Immunosuppression including calcineurin-inhibitors has been implicated in the acceleration of recurrent HCV. Recent studies suggest that outcomes may be better with cyclosporine (CSA-ME) compared to tacrolimus (TAC), but the data are inconclusive. We retrospectively analyzed data received from the United Network for Organ Sharing on 8809 chronic HCV liver transplant recipients receiving either cyclosporine microemulsion (CSA-ME) or tacrolimus (TAC) as maintenance immunosuppression prior to discharge. We analyzed patient death, graft failure, failure due recurrent disease and acute cellular rejection (ACR) for CSA-ME versus TAC treated patients. Three-year unadjusted patient and graft survival rates were 76.8% and 71.5%, respectively, in the CSA-ME group versus 79.9% and 75.0% in the TAC group. Propensity score-adjusted results suggest CSA-ME treated patients are at increased risk of patient death and graft failure [Hazards ratio (HR) = 1.17; 95% CI = 1.01-1.36 and HR = 1.19; 95% CI = 1.04-1.35, respectively] and biopsy-confirmed AR (HR = 2.03; 95% CI = 1.54-2.67) compared to TAC treated patients. These results provide evidence to reconsider the targeted administration of CSA-ME to HCV-infected liver transplant recipients.","DOI":"10.1111/j.1600-6143.2011.03508.x","ISSN":"1600-6143","note":"PMID: 21564522","shortTitle":"Cyclosporine versus tacrolimus treated liver transplant recipients with chronic hepatitis C","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Irish","given":"W D"},{"family":"Arcona","given":"S"},{"family":"Bowers","given":"D"},{"family":"Trotter","given":"J F"}],"issued":{"date-parts":[["2011",8]]},"PMID":"21564522"}}],"schema":""} [66]. Mycophenolate mofetil as an adjunct agent may have anti-HCV ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"k29es27ln","properties":{"formattedCitation":"{\\rtf \\super [67]\\nosupersub{}}","plainCitation":"[67]"},"citationItems":[{"id":436,"uris":[""],"uri":[""],"itemData":{"id":436,"type":"article-journal","title":"Mycophenolic acid inhibits hepatitis C virus replication and acts in synergy with cyclosporin A and interferon-alpha","container-title":"Gastroenterology","page":"1452-1462","volume":"131","issue":"5","source":"NCBI PubMed","abstract":"BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation. Clinical evidence suggests that particular immunosuppressive agents can have an influence on HCV recurrence. Cyclosporine A (CsA) specifically inhibits HCV replication through blocking the viral RNA polymerase enzyme NS5B. In this study, we investigated the effect of mycophenolic acid (MPA) and other immunosuppressants on HCV replication.\nMETHODS: MPA and other compounds were tested in vitro using an HCV-replication model containing a luciferase reporter gene.\nRESULTS: At clinically relevant concentrations (1.0-6.0 microg/mL), MPA inhibited HCV replication to approximately 75%. CsA and interferon (IFN)-alpha also showed inhibition in a dose-dependent manner. In these short-term (18 hours) experiments, MPA did not inhibit cell proliferation or induce cell death, which could have accounted for the antiviral effect. In contrast to the antiviral activity of MPA against West Nile virus, the effect of MPA on HCV replication was guanosine independent. When combined, MPA and CsA showed significant synergistic inhibition of replication, reaching maximum inhibition of approximately 90% at the highest doses. Synergistic effects were observed with suboptimal concentrations of IFN-alpha with MPA or CsA. The kinetics of HCV inhibition by MPA, CsA, and IFN-alpha were clearly distinct, with earliest effects seen with IFN-alpha. No specific inhibitory effects were observed with tacrolimus or rapamycin.\nCONCLUSIONS: The immunosuppressive drug MPA is as potent as CsA as an inhibitor of HCV replication. MPA was shown to have a distinct anti-HCV mechanism of action, independent of cell proliferation and guanosine depletion.","DOI":"10.1053/j.gastro.2006.08.027","ISSN":"0016-5085","note":"PMID: 17101321","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Henry","given":"Scot D"},{"family":"Metselaar","given":"Herold J"},{"family":"Lonsdale","given":"Richard C B"},{"family":"Kok","given":"Alice"},{"family":"Haagmans","given":"Bart L"},{"family":"Tilanus","given":"Hugo W"},{"family":"van der Laan","given":"Luc J W"}],"issued":{"date-parts":[["2006",11]]},"PMID":"17101321"}}],"schema":""} [67] and anti HIV effects ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qG2AbWyU","properties":{"formattedCitation":"{\\rtf \\super [68,69]\\nosupersub{}}","plainCitation":"[68,69]"},"citationItems":[{"id":434,"uris":[""],"uri":[""],"itemData":{"id":434,"type":"article-journal","title":"Inhibition of HIV replication in vitro by clinical immunosuppressants and chemotherapeutic agents","container-title":"Cell & bioscience","page":"22","volume":"3","issue":"1","source":"NCBI PubMed","abstract":"BACKGROUND: Recent studies have suggested that a functional cure for HIV-1 infection, purportedly resultant from allogeneic bone marrow transplantation, may be possible. Additionally, the first such patient was treated with whole-body irradiation, immunosuppressants, and the chemotherapeutic, cytarabine. However, the precise role of the coinciding medical interventions in diminishing detectable HIV reservoirs remains unstudied.\nFINDINGS: In this article, we demonstrate that the immunosuppressants, mycophenolic acid and cyclosporine, and the chemotherapeutic, cytarabine, are potent antiretroviral agents at clinically relevant dosages. These drugs strongly inhibit HIV-1 replication in a GFP indicator T cell line and peripheral blood mononuclear cells (PBMC).\nCONCLUSIONS: Our study suggests that certain clinical immunosuppressants and chemotherapeutic agents may act combinatorially to inhibit HIV infection. Additionally, chemotherapy-mediated cytotoxicity may also affect the stability of viral reservoirs. Thus, further study is needed to examine potential therapeutic value of these interventions in patients.","DOI":"10.1186/2045-3701-3-22","ISSN":"2045-3701","note":"PMID: 23672887","journalAbbreviation":"Cell Biosci","language":"eng","author":[{"family":"Hawley","given":"Todd"},{"family":"Spear","given":"Mark"},{"family":"Guo","given":"Jia"},{"family":"Wu","given":"Yuntao"}],"issued":{"date-parts":[["2013"]]},"PMID":"23672887"}},{"id":438,"uris":[""],"uri":[""],"itemData":{"id":438,"type":"article-journal","title":"The addition of mycophenolate mofetil to antiretroviral therapy including abacavir is associated with depletion of intracellular deoxyguanosine triphosphate and a decrease in plasma HIV-1 RNA","container-title":"Journal of acquired immune deficiency syndromes (1999)","page":"45-49","volume":"31","issue":"1","source":"NCBI PubMed","abstract":"Mycophenolic acid (MPA) enhances the in vitro activity of abacavir (ABC) and other nucleoside analog reverse transcriptase inhibitors (NRTIs) against sensitive and NRTI-resistant HIV-1. This may occur via depletion of intracellular deoxyguanosine triphosphate (dGTP). Mycophenolate mofetil (MMF) 500 mg twice daily was added as a single agent to the antiretroviral regimens of five patients failing maximal available therapy. Therapy included ABC, and in most cases didanosine (DDI) and tenofovir (TDF). At entry, mean plasma HIV-1 RNA (VL) was 5.02 log copies/mL (median 4.78, range 4.71-5.63) and mean CD4 count was 106/microL (median 117, range 11-174). MMF was well tolerated. CD4 cell counts did not change significantly from baseline for up to 60 weeks of follow-up. Three of five subjects had VL declines of >0.5 log copies/mL immediately after adding MMF; a fourth subject had a sustained decline of >0.5 log copies/mL after week 8. Declines of >0.5 log copies/mL were lost in two patients at 6 and 8 weeks, and persisted in two patients at 36 and 60 weeks of follow-up, respectively. An increase in the ratio of carbovir triphosphate (CBV-TP), the active antiviral metabolite of ABC, to dGTP was documented in 3 of 4 subjects in temporal association with decreased VL. Trough plasma MPA levels ranged from 0.26-1.67 microg/mL; peak levels 90 minutes after dosing from 1.20-7.77 microg/mL. AUC of MPA appeared little changed when measured over 28 weeks of therapy. Declines in VL were observed in association with measurable changes in the CBV-TP/dGTP ratio in some patients, whereas MPA AUC was below the 30-60 microg*hr/mL range targeted in organ transplantation. The possibility that MMF may enhance the effect of selected NRTIs and be tolerated in late stage HIV disease deserves careful randomized study.","ISSN":"1525-4135","note":"PMID: 12352149","journalAbbreviation":"J. Acquir. Immune Defic. Syndr.","language":"eng","author":[{"family":"Margolis","given":"David M"},{"family":"Kewn","given":"Stephen"},{"family":"Coull","given":"Jason J"},{"family":"Ylisastigui","given":"Loyda"},{"family":"Turner","given":"Diana"},{"family":"Wise","given":"Holly"},{"family":"Hossain","given":"Mohammed M"},{"family":"Lanier","given":"E Randall"},{"family":"Shaw","given":"Leslie M"},{"family":"Back","given":"David"}],"issued":{"date-parts":[["2002",9,1]]},"PMID":"12352149"}}],"schema":""} [68,69]. Sirolimus may be considered as a calcineurin inhibitor-sparing agent in the context of renal insufficiency. As well, sirolimus may reduce HIV replication through blocking of the HIV entry receptor, CCR5 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"9fjmms43k","properties":{"formattedCitation":"{\\rtf \\super [70]\\nosupersub{}}","plainCitation":"[70]"},"citationItems":[{"id":440,"uris":[""],"uri":[""],"itemData":{"id":440,"type":"article-journal","title":"Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV beta-chemokines: an approach to suppress R5 strains of HIV-1","container-title":"Proceedings of the National Academy of Sciences of the United States of America","page":"10411-10416","volume":"100","issue":"18","source":"NCBI PubMed","abstract":"Propagation of R5 strains of HIV-1 on CD4 lymphocytes and macrophages requires expression of the CCR5 coreceptor on the cell surface. Individuals lacking CCR5 (CCR5 Delta 32 homozygous genotype) are phenotypically normal and resistant to infection with HIV-1. CCR5 expression on lymphocytes depends on signaling through the IL-2 receptor. By FACS analysis we demonstrate that rapamycin (RAPA), a drug that disrupts IL-2 receptor signaling, reduces CCR5 surface expression on T cells at concentrations as low as 1 nM. In addition, lower concentrations of RAPA (0.01 nM) were sufficient to reduce CCR5 surface expression on maturing monocytes. PCR analysis on peripheral blood mononuclear cells (PBMCs) showed that RAPA interfered with CCR5 expression at the transcriptional level. Reduced expression of CCR5 on PBMCs cultured in the presence of RAPA was associated with increased extracellular levels of macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. In infectivity assays, RAPA suppressed the replication of R5 strains of HIV-1 both in PBMC and macrophage cultures. In total PBMC cultures, RAPA-mediated inhibition of CCR5-using strains of HIV-1 occurred at 0.01 nM, a concentration of drug that is approximately 103 times lower than therapeutic through levels of drug in renal transplant recipients. In addition, RAPA enhanced the antiviral activity of the CCR5 antagonist TAK-779. These results suggest that low concentrations of RAPA may have a role in both the treatment and prevention of HIV-1 infection.","DOI":"10.1073/pnas.1834278100","ISSN":"0027-8424","note":"PMID: 12915736","shortTitle":"Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV beta-chemokines","journalAbbreviation":"Proc. Natl. Acad. Sci. U.S.A.","language":"eng","author":[{"family":"Heredia","given":"A"},{"family":"Amoroso","given":"A"},{"family":"Davis","given":"C"},{"family":"Le","given":"N"},{"family":"Reardon","given":"E"},{"family":"Dominique","given":"J K"},{"family":"Klingebiel","given":"E"},{"family":"Gallo","given":"R C"},{"family":"Redfield","given":"R R"}],"issued":{"date-parts":[["2003",9,2]]},"PMID":"12915736"}}],"schema":""} [70], has antitumor properties in HCC ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1ko4s63nd","properties":{"formattedCitation":"{\\rtf \\super [71]\\nosupersub{}}","plainCitation":"[71]"},"citationItems":[{"id":444,"uris":[""],"uri":[""],"itemData":{"id":444,"type":"article-journal","title":"Meta-analysis: recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma","container-title":"Alimentary pharmacology & therapeutics","page":"411-419","volume":"37","issue":"4","source":"NCBI PubMed","abstract":"BACKGROUND: The use of sirolimus (SRL)-based immunosuppression protocols have been reported to reduce recurrence rates following liver transplantation (LT) for hepatocellular carcinoma (HCC), although this is still a matter for debate.\nAIM: To undertake a systematic review and meta-analysis of available literature on the usage of SRL as an immunosuppressive agent following LT for HCC, with a view to comparing cancer outcomes with the commonly used calcineurin inhibitors (CNIs).\nMETHODS: Systematic review and meta-analysis carried out in line with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Primary outcomes of interest were tumour recurrence rate and recurrence-free survival (RFS). Secondary outcomes were recurrence-related mortality and overall survival (OS).\nRESULTS: In all, 5 studies met the inclusion criteria (n = 474). The recurrence rate was lower in SRL group (4.9-12.9%) in comparison with CNIs (17.3-38.7%). The 1-, 3- and 5-year RFS was 93-96%, 82-86% and 79-80% for SRL group, which was much better in comparison with the CNIs 70-78%, 64-65% and 54-60% respectively. Similarly, 1-, 3- and 5-year OS was much better for SRL group (94-95%, 85% and 80%) in comparison with CNIs (79-83%, 66% and 59-62%) respectively. Meta-analysis demonstrated lower recurrence (OR = 0.30, 95% CI = 0.16-0.55, P < 0.001), lower recurrence-related mortality (OR = 0.29, 95% CI = 0.12-0.70, P = 0.005) and lower overall mortality (OR = 0.35, 95% CI = 0.20-0.61, P < 0.001) for SRL group.\nCONCLUSION: The review showed lower recurrence rate, longer recurrence-free survival and overall survival and lower recurrence-related mortality in sirolimus-treated patients in comparison with the calcineurin inhibitor-treated patients following liver transplantation for hepatocellular carcinoma.","DOI":"10.1111/apt.12185","ISSN":"1365-2036","note":"PMID: 23278125","shortTitle":"Meta-analysis","journalAbbreviation":"Aliment. Pharmacol. Ther.","language":"eng","author":[{"family":"Menon","given":"K V"},{"family":"Hakeem","given":"A R"},{"family":"Heaton","given":"N D"}],"issued":{"date-parts":[["2013",2]]},"PMID":"23278125"}}],"schema":""} [71] and demonstrated improved outcomes in a small series of HIV/HCV coinfected patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1s8umvdn8v","properties":{"formattedCitation":"{\\rtf \\super [72]\\nosupersub{}}","plainCitation":"[72]"},"citationItems":[{"id":442,"uris":[""],"uri":[""],"itemData":{"id":442,"type":"article-journal","title":"First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation","container-title":"Transplantation","page":"733-738","volume":"89","issue":"6","source":"NCBI PubMed","abstract":"INTRODUCTION: Some experimental trials have demonstrated that rapamycin (RAPA) is able to inhibit HIV-1 progression in three different ways: (1) reducing CCR5-gene transcription, (2) blocking interleukin-2 intracellular secondary messenger (mammalian target of rapamycin), and (3) up-regulating the beta-chemokine macrophage inflammatory protein (MIP; MIP-1alpha and MIP-1beta). We present the preliminary results of a prospective nonrandomized trial concerning the first HIV patient series receiving RAPA monotherapy after liver transplantation (LT).\nMETHODS: Since June 2003, 14 HIV patients have received cadaveric donor LT due to end-stage liver disease (ESLD) associated or not associated with hepatocellular carcinoma, scored by the model for ESLD system. Patients were assessed using the following criteria for HIV characterization: CD4 T-cell count more than 100/mL and HIV-RNA levels less than 50 copies/mL. Primary immunosuppression was based on calcineurin inhibitors (CI), whereas switch to RAPA monotherapy occurred in cases of CI complications or Kaposi's sarcoma.\nRESULTS: Mean overall post-LT follow-up was 14.8 months (range: 0.5-52.6). Six of 14 patients were administered RAPA monotherapy. Mean preswitch period from CI to RAPA was 67 days (range: 10-225 days). Mean postswitch follow-up was 11.9 months (range: 2-31 months). All patients were affected by ESLD, which was associated with hepatocellular carcinoma in seven patients. ESLD occurred due to hepatitis C virus (HCV)-related hepatopathy for nine patients, hepatitis B virus-related hepatopathy for one patient, and hepatitis B virus-HCV hepatopathy for four patients. Significantly better control of HIV and HCV replication was found among patients taking RAPA monotherapy (P=0.0001 and 0.03, respectively).\nCONCLUSIONS: After in vitro and in vivo experimental evidence of RAPA antiviral proprieties, to our knowledge, this is the first clinical report of several significant benefits in long-term immunosuppression maintenance and HIV-1 control among HIV positive patients who underwent LT.","DOI":"10.1097/TP.0b013e3181c7dcc0","ISSN":"1534-6080","note":"PMID: 20048692","journalAbbreviation":"Transplantation","language":"eng","author":[{"family":"Di Benedetto","given":"Fabrizio"},{"family":"Di Sandro","given":"Stefano"},{"family":"De Ruvo","given":"Nicola"},{"family":"Montalti","given":"Roberto"},{"family":"Ballarin","given":"Roberto"},{"family":"Guerrini","given":"Gian Piero"},{"family":"Spaggiari","given":"Mario"},{"family":"Guaraldi","given":"Giovanni"},{"family":"Gerunda","given":"Giorgio"}],"issued":{"date-parts":[["2010",3,27]]},"PMID":"20048692"}}],"schema":""} [72]. However, analysis of the Scientific Registry of Transplant Recipients database showed worse graft survival and overall HCV patient survival ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"28sql0oekk","properties":{"formattedCitation":"{\\rtf \\super [73]\\nosupersub{}}","plainCitation":"[73]"},"citationItems":[{"id":452,"uris":[""],"uri":[""],"itemData":{"id":452,"type":"article-journal","title":"Impact of sirolimus and tacrolimus on mortality and graft loss in liver transplant recipients with or without hepatitis C virus: an analysis of the Scientific Registry of Transplant Recipients Database","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"1029-1036","volume":"18","issue":"9","source":"NCBI PubMed","abstract":"By analyzing 26,414 patients [12,589 with hepatitis C virus (HCV)] in the Scientific Registry of Transplant Recipients Database, we sought to determine comparative risk factors (including primary immunosuppression) predictive of death and graft loss among patients with HCV and patients without HCV. Immunosuppression was examined at the baseline and as a time-dependent variable, and the results were stratified by the transplant center and were adjusted for variables well known to affect patient and graft survival. A multivariate analysis of patient mortality demonstrated that recipient age, donor age, hepatocellular carcinoma, diabetes, and creatinine were significantly associated with increased 3-year mortality for both groups. Tacrolimus-based immunosuppression was associated with superior survival in both groups. In contrast, the use of sirolimus was strongly associated with increased mortality in the HCV group, and cyclosporine was associated with increased mortality in the non-HCV group. Adjusting for known and unknown factors predictive of posttransplant outcomes, a propensity analysis confirmed the association of sirolimus use with an increased risk of death in HCV patients as well as the association of tacrolimus use with a decreased risk of death in all patients. In conclusion, this study suggests a novel association between sirolimus use and an increased risk of death and graft loss after liver transplantation in HCV patients that is not seen in patients without HCV. This study confirms the association of tacrolimus with superior outcomes. Sirolimus should be used sparingly in recipients with HCV infections.","DOI":"10.1002/lt.23479","ISSN":"1527-6473","note":"PMID: 22641474","shortTitle":"Impact of sirolimus and tacrolimus on mortality and graft loss in liver transplant recipients with or without hepatitis C virus","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Watt","given":"Kymberly D"},{"family":"Dierkhising","given":"Ross"},{"family":"Heimbach","given":"Julie K"},{"family":"Charlton","given":"Michael R"}],"issued":{"date-parts":[["2012",9]]},"PMID":"22641474"}}],"schema":""} [73] as well as an increased risk of hepatic artery thrombosis ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2gg2npila4","properties":{"formattedCitation":"{\\rtf \\super [74]\\nosupersub{}}","plainCitation":"[74]"},"citationItems":[{"id":446,"uris":[""],"uri":[""],"itemData":{"id":446,"type":"article-journal","title":"Multicentric outcome analysis of sirolimus-based immunosuppression in 252 liver transplant recipients","container-title":"Transplant international: official journal of the European Society for Organ Transplantation","page":"155-168","volume":"23","issue":"2","source":"NCBI PubMed","abstract":"SUMMARY: The use of sirolimus (SRL) in orthotopic liver transplantation (OLT) has been controversial after experimental data suggested an increased risk of hepatic artery thrombosis (HAT). To assess the safety and efficacy of SRL as de novo immunosuppression in OLT recipients. Outcomes of 252 OLT patients who received SRL were compared with outcomes of 291 OLT recipients who received calcineurin inhibitor in a retrospective study. Primary outcomes of this study were: patient- and graft survivals, vascular, biliary, wound complications and rejection rates. Secondary outcomes were: postoperative infection rate, bone marrow and renal function and changes of lipid levels. Patient- and graft survivals, rejection and infection rates were similar. In the SRL group, HAT occurred in 1.2%, biliary complications in 19.4%, and incisional hernias in 9.1%. In the control group the incidence of HAT was 5.8% (P = 0.004), biliary complications 18.5% (P = NS) and incisional hernias 7.2% (P = NS). Patients on SRL experienced significantly higher levels of serum triglycerides but fewer acute cellular rejections. Bone marrow and renal functions were similar in both the groups. Our findings would suggest that SRL is safe and effective for very selected OLT recipients. Randomized controlled trials are necessary to confirm our results.","DOI":"10.1111/j.1432-2277.2009.00969.x","ISSN":"1432-2277","note":"PMID: 19765266","journalAbbreviation":"Transpl. Int.","language":"eng","author":[{"family":"Molinari","given":"Michele"},{"family":"Berman","given":"Kenneth"},{"family":"Meeberg","given":"Glenda"},{"family":"Shapiro","given":"James A"},{"family":"Bigam","given":"David"},{"family":"Trotter","given":"James F"},{"family":"Kneteman","given":"Norman"}],"issued":{"date-parts":[["2010",2]]},"PMID":"19765266"}}],"schema":""} [74]. Thus the risk-benefit ratio of sirolimus will need to be carefully considered. Medication management in HIV positive transplant recipients is challenging due to bidirectional drug interactions between immunosuppressants and antiretrovirals which may lead to altered drug exposure, toxicity, rejection or poorly controlled HIV ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2fh0eibeq8","properties":{"formattedCitation":"{\\rtf \\super [75]\\nosupersub{}}","plainCitation":"[75]"},"citationItems":[{"id":337,"uris":[""],"uri":[""],"itemData":{"id":337,"type":"article-journal","title":"Drug-drug interactions between antiretroviral and immunosuppressive agents in HIV-infected patients after solid organ transplantation: a review","container-title":"AIDS patient care and STDs","page":"568-581","volume":"26","issue":"10","source":"NCBI PubMed","abstract":"Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive therapy proved to be extremely challenging, as witnessed by high rates of allograft rejection and drug toxicity, but the profound drug-drug interactions between immunosuppressants and cART, especially protease inhibitors (PIs) also play an important role. Caution and frequent drug level monitoring of calcineurin inhibitors, such as tacrolimus are necessary when PIs are (re)introduced or withdrawn in HIV-infected recipients. Furthermore, the pharmacokinetics of glucocorticoids and mTOR inhibitors are seriously affected by PIs. With the introduction of integrase inhibitors, CCR5-antagonists and fusion inhibitors which cause significantly less pharmacokinetic interactions, have minor overlapping toxicity, and offer the advantage of pharmacodynamic synergy, it is time to revaluate what may be considered the optimal antiretroviral regimen in SOT recipients. In this review we provide a brief overview of the recent success of SOT in the HIV population, and an update on the pharmacokinetic and pharmacodynamic interactions between currently available cART and immunosuppressants in HIV-infected patients, who underwent SOT.","DOI":"10.1089/apc.2012.0169","ISSN":"1557-7449","note":"PMID: 23025916","shortTitle":"Drug-drug interactions between antiretroviral and immunosuppressive agents in HIV-infected patients after solid organ transplantation","journalAbbreviation":"AIDS Patient Care STDS","language":"eng","author":[{"family":"van Maarseveen","given":"Erik M"},{"family":"Rogers","given":"Christin C"},{"family":"Trofe-Clark","given":"Jennifer"},{"family":"van Zuilen","given":"Arjan D"},{"family":"Mudrikova","given":"Tania"}],"issued":{"date-parts":[["2012",10]]},"PMID":"23025916"}}],"schema":""} [75]. Close communication between pharmacists managing the HIV antivirals and immunosuppression will be critical. Therefore, both the HIV team and the transplant teams should be informed about any medication changes. Antiretroviral therapy should be given up to the time of transplant and then restarted as soon as possible post transplant once oral therapy is tolerated and ideally no longer than a week post operatively; generally in well suppressed patients before transplant, the HIV viral loads will not rebound within that time-frame. If there is poor oral absorption, HAART levels may be sub-therapeutic leading to increased risk of resistance and viral breakthrough. The key drug-drug interactions are summarized in Table 4.ProphylaxisIn HBV patients post transplant, most patients initially receive HBIG as prophylaxis for recurrent infection ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"265dhst7vv","properties":{"formattedCitation":"{\\rtf \\super [76]\\nosupersub{}}","plainCitation":"[76]"},"citationItems":[{"id":268,"uris":[""],"uri":[""],"itemData":{"id":268,"type":"article-journal","title":"Hepatitis B immunoglobulin for prevention of hepatitis B virus infection and recurrence after liver transplantation","container-title":"Expert review of clinical immunology","page":"429-436","volume":"7","issue":"4","source":"NCBI PubMed","abstract":"Intravenous hepatitis B immunoglobulin (HBIG) is a human plasma-derived purified gammaglobulin (IgG) that has proven efficacy and dose-dependent response in the prevention of hepatitis B virus (HBV) recurrence after liver transplantation. It is also indicated for postexposure prophylaxis after contact with blood or body fluids of serum hepatitis B surface antigen (HBsAg)-positive carriers and in prevention of mother-to-child (vertical) transmission. The exact mechanism of passive immunization is unknown; HBIG may block HBV entry and binding to hepatocytes, neutralize circulating HBV and target HBV-infected cells through an antibody-mediated immune response. The drug is well tolerated and common side effects include fever, chills and arthralgias that are usually mild and transient. This article summarizes the main indications and the recommendations for use of intravenous HBIG, as well as the usage of intramuscular HBIG in the liver transplant setting.","DOI":"10.1586/eci.11.30","ISSN":"1744-8409","note":"PMID: 21790285","journalAbbreviation":"Expert Rev Clin Immunol","language":"eng","author":[{"family":"Congly","given":"Stephen E"},{"family":"Burak","given":"Kelly W"},{"family":"Coffin","given":"Carla S"}],"issued":{"date-parts":[["2011",7]]},"PMID":"21790285"}}],"schema":""} [76]. The use of a potent HBV medication such as tenofovir or entecavir is also recommended. Likely, with suppression of HBV with a newer nucleos(t)ide analogue, HBIG may be able to be stopped in many patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"LaW4JFPQ","properties":{"formattedCitation":"{\\rtf \\super [77\\uc0\\u8211{}79]\\nosupersub{}}","plainCitation":"[77–79]"},"citationItems":[{"id":460,"uris":[""],"uri":[""],"itemData":{"id":460,"type":"article-journal","title":"Nucleoside plus nucleotide analogs and cessation of hepatitis B immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective","container-title":"Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology","page":"67-73","volume":"58","issue":"1","source":"NCBI PubMed","abstract":"BACKGROUND: After orthotopic liver transplantation (OLT) in chronic hepatitis B (HBV), adequate prophylaxis for recurrence of HBV in the graft is mandatory.\nOBJECTIVES: Evaluate safety of HBV prophylaxis with tenofovir and emtricitabine (TDF/FTC) after cessation of hepatitis B immunoglobulin (HBIG) after OLT in chronic HBV.\nSTUDY DESIGN: In 17 consecutive patients after OLT in chronic HBV we started TDF/FTC after cessation of HBIG. All had received HBIG >6 months. 15/17 were HBsAg negative and 16/17 had undetectable HBV-DNA.\nRESULTS: After mean follow-up of 2 years 16/17 patients were alive, one died due to urosepsis. All 16 with undetectable HBV-DNA remained HBV-DNA negative. From 15 HBsAg negative patients at start, in one seroconversion to positive HBsAg occurred, without detectable HBV-DNA. Liver biochemistry remained within the normal ranges. There were no cases of drug discontinuation. No major side effects were reported. TDF/FTC use saves €16,262/year over standard-of-care (HBIG+LAM). This prospective follow-up study shows that in liver transplantation for chronic hepatitis B, after initial treatment including HBIG for at least 6 months combined with or followed by (dual) nucleos(t)ide analog therapy, TDF/FTC provides adequate prophylaxis against recurrent HBV infection without major side effects and leads to substantial cost savings over a regimen with HBIG.\nCONCLUSION: Combined prophylaxis with TDF/ETV nucleoside plus nucleotide analogs and cessation of immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective.","DOI":"10.1016/j.jcv.2013.06.035","ISSN":"1873-5967","note":"PMID: 23880162","journalAbbreviation":"J. Clin. Virol.","language":"eng","author":[{"family":"Wesdorp","given":"D J W"},{"family":"Knoester","given":"M"},{"family":"Braat","given":"A E"},{"family":"Coenraad","given":"M J"},{"family":"Vossen","given":"A C T M"},{"family":"Claas","given":"E C J"},{"family":"van Hoek","given":"B"}],"issued":{"date-parts":[["2013",9]]},"PMID":"23880162"}},{"id":462,"uris":[""],"uri":[""],"itemData":{"id":462,"type":"article-journal","title":"Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B","container-title":"The American journal of gastroenterology","page":"942-948","volume":"108","issue":"6","source":"NCBI PubMed","abstract":"OBJECTIVES: The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone.\nMETHODS: A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up.\nRESULTS: Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients.\nCONCLUSIONS: Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.","DOI":"10.1038/ajg.2013.111","ISSN":"1572-0241","note":"PMID: 23629601","journalAbbreviation":"Am. J. Gastroenterol.","language":"eng","author":[{"family":"Fung","given":"James"},{"family":"Chan","given":"See-Ching"},{"family":"Cheung","given":"Cindy"},{"family":"Yuen","given":"Man-Fung"},{"family":"Chok","given":"Kenneth Siu-Ho"},{"family":"Sharr","given":"William"},{"family":"Chan","given":"Albert Chi-Yan"},{"family":"Cheung","given":"Tan-To"},{"family":"Seto","given":"Wai-Kay"},{"family":"Fan","given":"Sheung-Tat"},{"family":"Lai","given":"Ching-Lung"},{"family":"Lo","given":"Chung-Mau"}],"issued":{"date-parts":[["2013",6]]},"PMID":"23629601"}},{"id":464,"uris":[""],"uri":[""],"itemData":{"id":464,"type":"article-journal","title":"Randomized trial of emtricitabine/tenofovir disoproxil fumarate after hepatitis B immunoglobulin withdrawal after liver transplantation","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"594-601","volume":"19","issue":"6","source":"NCBI PubMed","abstract":"Long-term prophylaxis with hepatitis B immunoglobulin (HBIG) for the prevention of hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) in patients with chronic HBV infection is inconvenient and costly. This randomized, prospective phase 2 study compared emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) after HBIG withdrawal to FTC/TDF plus HBIG for the prevention of HBV recurrence after OLT. Forty patients with a median time since liver transplantation of 3.4 years (interquartile range?=?1.9-5.6 years) received 24 weeks of open-label FTC/TDF plus HBIG before randomization. Patients who maintained confirmed viral suppression were randomized to continue FTC/TDF plus HBIG (n?=?19) or receive FTC/TDF alone (n?=?18) for an additional 72 weeks. No patient experienced HBV recurrence through 72 weeks of the study while he or she was receiving the randomized treatment. Both treatment arms were safe and well tolerated; no serious or severe drug-related adverse events were observed. Renal function was consistent with that observed in a posttransplant population. The withdrawal of HBIG after 6 months' treatment with FTC/TDF should be considered in liver transplant recipients to prevent chronic HBV recurrence.","DOI":"10.1002/lt.23628","ISSN":"1527-6473","note":"PMID: 23447407","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Teperman","given":"Lewis W"},{"family":"Poordad","given":"Fred"},{"family":"Bzowej","given":"Natalie"},{"family":"Martin","given":"Paul"},{"family":"Pungpapong","given":"Surakit"},{"family":"Schiano","given":"Thomas"},{"family":"Flaherty","given":"John"},{"family":"Dinh","given":"Phillip"},{"family":"Rossi","given":"Stephen"},{"family":"Subramanian","given":"G Mani"},{"family":"Spivey","given":"James"}],"issued":{"date-parts":[["2013",6]]},"PMID":"23447407"}}],"schema":""} [77–79] or may not even be required ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"lulckccku","properties":{"formattedCitation":"{\\rtf \\super [80]\\nosupersub{}}","plainCitation":"[80]"},"citationItems":[{"id":466,"uris":[""],"uri":[""],"itemData":{"id":466,"type":"article-journal","title":"Combination of lamivudine and adefovir without hepatitis B immune globulin is safe and effective prophylaxis against hepatitis B virus recurrence in hepatitis B surface antigen-positive liver transplant candidates","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"268-274","volume":"19","issue":"3","source":"NCBI PubMed","abstract":"Without effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related liver disease is frequently complicated by severe and rapidly progressive HBV recurrence. Combination prophylaxis with hepatitis B immune globulin (HBIG) and lamivudine (LAM) reduces long-term recurrence rates below 10%; however, HBIG is costly and inconvenient to administer. We, therefore, conducted a multicenter, prospective study of outcomes with an HBIG-sparing regimen of LAM plus adefovir dipivoxil (ADV) initiated at the time of listing for liver transplantation and continued after transplantation. Twenty-six patients were recruited into this study at the time of listing for transplantation, and 20 subsequently underwent transplantation. Twelve of the 26 patients had LAM exposure before the study baseline, but none had LAM resistance. The median HBV viral load before the institution of antiviral therapy was approximately 4.0 log(10) IU/mL (range=2.3-7.5 log(10) IU/mL). To the 20 patients who underwent transplantation, 800 IU of intramuscular HBIG was given immediately after transplantation and daily for 7 days only (total HBIG dose=6400 IU). All transplant patients remained alive without HBV recurrence (they were negative for hepatitis B surface antigen, and HBV DNA was undetectable) after a median follow-up of 57 months after transplantation (range=27-83 months). The median serum creatinine level in these patients rose from 81 to 119 μmol/L over the course of the study. No patient required dose reduction or cessation. After the completion of this prospective study, the regimen was modified so that no perioperative HBIG was administered if the pretransplant serum HBV DNA level was suppressed below 3 log(10) IU/mL. Another 28 patients with HBV-related liver disease underwent transplantation (18 without HBIG). All remained alive and well without HBV recurrence after a median follow-up of 22 months after transplantation (range=10-58 months). In conclusion, a combination of LAM and ADV initiated at the time of wait listing provides safe and effective protection against recurrent HBV infection without the high costs and inconvenience associated with long-term HBIG therapy.","DOI":"10.1002/lt.23600","ISSN":"1527-6473","note":"PMID: 23447403","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Gane","given":"Edward J"},{"family":"Patterson","given":"Scott"},{"family":"Strasser","given":"Simone I"},{"family":"McCaughan","given":"Geoffrey W"},{"family":"Angus","given":"Peter W"}],"issued":{"date-parts":[["2013",3]]},"PMID":"23447403"}}],"schema":""} [80]. In the context of a HBV-HIV co-infected patient, until further data exists with regards to HBIG sparing therapy, we would use HBIG in combination with tenofovir or entecavir with consideration of indefinite HBIG use due to a high incidence of occult HBV post liver transplant as well as to account for possible anti-HBV drug interruptions.Given the immunodeficiency from the HIV as well as the antirejection medication, infection prophylaxis is critical (Table 5). From an infection standpoint, perioperative prophylaxis to cover gastrointestinal pathogens, including Enterococcus, as well as Candida in those at high risk, in addition to cytomegalovirus prophylaxis with valganciclovir is identical to patients without HIV. All co-infected patients should remain on lifelong prophylaxis for Pneumocystis jirovecii pneumonia with one tablet of single strength trimethoprim/sulfamethoxazole daily. For those intolerant, alternatives include monthly inhaled pentamidine, oral dapsone or atovaquone. Summary of post transplant management issues in HIV/viral hepatitis co-infectionRejection: Patients with HIV are at increased risks of acute cellular rejection ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2mkrntorv9","properties":{"formattedCitation":"{\\rtf \\super [2,41]\\nosupersub{}}","plainCitation":"[2,41]"},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"716-726","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.","DOI":"10.1002/lt.23411","ISSN":"1527-6473","note":"PMID: 22328294","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Terrault","given":"Norah A"},{"family":"Roland","given":"Michelle E"},{"family":"Schiano","given":"Thomas"},{"family":"Dove","given":"Lorna"},{"family":"Wong","given":"Michael T"},{"family":"Poordad","given":"Fred"},{"family":"Ragni","given":"Margaret V"},{"family":"Barin","given":"Burc"},{"family":"Simon","given":"David"},{"family":"Olthoff","given":"Kim M"},{"family":"Johnson","given":"Lynt"},{"family":"Stosor","given":"Valentina"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Fung","given":"John"},{"family":"Sherman","given":"Kenneth E"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Slakey","given":"Douglas"},{"family":"Berg","given":"Carl L"},{"family":"Carlson","given":"Laurie"},{"family":"Ferrell","given":"Linda"},{"family":"Stablein","given":"Donald M"},{"family":"Odim","given":"Jonah"},{"family":"Fox","given":"Lawrence"},{"family":"Stock","given":"Peter G"},{"family":"Solid Organ Transplantation in HIV: Multi-Site Study Investigators","given":""}],"issued":{"date-parts":[["2012",6]]},"PMID":"22328294"}},{"id":311,"uris":[""],"uri":[""],"itemData":{"id":311,"type":"article-journal","title":"Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1866-1876","volume":"12","issue":"7","source":"NCBI PubMed","abstract":"Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.","DOI":"10.1111/j.1600-6143.2012.04028.x","ISSN":"1600-6143","note":"PMID: 22471341","shortTitle":"Outcome of HCV/HIV-coinfected liver transplant recipients","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Miro","given":"J M"},{"family":"Montejo","given":"M"},{"family":"Castells","given":"L"},{"family":"Rafecas","given":"A"},{"family":"Moreno","given":"S"},{"family":"Agüero","given":"F"},{"family":"Abradelo","given":"M"},{"family":"Miralles","given":"P"},{"family":"Torre-Cisneros","given":"J"},{"family":"Pedreira","given":"J D"},{"family":"Cordero","given":"E"},{"family":"de la Rosa","given":"G"},{"family":"Moyano","given":"B"},{"family":"Moreno","given":"A"},{"family":"Perez","given":"I"},{"family":"Rimola","given":"A"},{"family":"Spanish OLT in HIV-Infected Patients Working Group investigators","given":""}],"issued":{"date-parts":[["2012",7]]},"PMID":"22471341"}}],"schema":""} [2,41]; careful monitoring is required. Given the increased risk, protocol biopsies are recommended peritransplant at baseline, 6 mo, 12 mo and then annually subsequently. When rejection is clinically suspected, a biopsy should be obtained. The preferred method to treat rejection is to increase calcineurin inhibitor levels or sirolimus levels depending on the agent being used, as well as increasing mycophenolate mofetil levels. Use of anti-lymphocyte depleting agents, such as thymoglobulin, is to be avoided if possible due to prolonged immunosuppression of T cells with thymoglobulin ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"3q2acf2as","properties":{"formattedCitation":"{\\rtf \\super [81]\\nosupersub{}}","plainCitation":"[81]"},"citationItems":[{"id":468,"uris":[""],"uri":[""],"itemData":{"id":468,"type":"article-journal","title":"Thymoglobulin-associated Cd4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"753-760","volume":"6","issue":"4","source":"NCBI PubMed","abstract":"HIV-infected patients are increasingly referred for kidney transplantation, and may be at an increased risk for rejection. Treatment for rejection frequently includes thymoglobulin. We studied thymoglobulin's effect on CD4+ T-cell count, risk of infection and rejection reversal in 20 consecutive HIV-infected kidney recipients. All patients used antiretroviral therapy and opportunistic infection prophylaxis. Maintenance immunosuppression consisted of prednisone, mycophenolate mofetil and cyclosporine. Eleven patients received thymoglobulin (7 for rejection and 4 for delayed/slow graft function) while 9 did not. These two groups were similar in age, gender, race, donor characteristics and immunosuppression. Mean CD4+ T-cell counts remained stable in patients who did not receive thymoglobulin, but became profoundly suppressed in those who did, decreasing from 475 +/- 192 to 9 +/- 10 cells/microL (p < 0.001). Recovery time ranged from 3 weeks to 2 years despite effective HIV suppression. Although opportunistic infections were successfully suppressed, low CD4+ T-cell count was associated with increased risk of serious infections requiring hospitalization. Rejection reversed in 6 of 7 patients receiving thymoglobulin. We conclude that thymoglobulin reverses acute rejection in HIV-infected kidney recipients, but produces profound and long-lasting suppression of the CD4+ T-cell count associated with increased risk of infections requiring hospitalization.","DOI":"10.1111/j.1600-6143.2006.01238.x","ISSN":"1600-6135","note":"PMID: 16539632","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Carter","given":"J T"},{"family":"Melcher","given":"M L"},{"family":"Carlson","given":"L L"},{"family":"Roland","given":"M E"},{"family":"Stock","given":"P G"}],"issued":{"date-parts":[["2006",4]]},"PMID":"16539632"}}],"schema":""} [81]. High dose steroids in the context of HCV co-infection leads to more aggressive disease activity and rapid progression in fibrosis ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1flkk6rk7r","properties":{"formattedCitation":"{\\rtf \\super [82]\\nosupersub{}}","plainCitation":"[82]"},"citationItems":[{"id":470,"uris":[""],"uri":[""],"itemData":{"id":470,"type":"article-journal","title":"Immunosuppression, liver injury and post-transplant HCV recurrence","container-title":"Journal of viral hepatitis","page":"1-8","volume":"19","issue":"1","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) infection is a major cause for liver transplantation worldwide. Still, HCV re-infection of the graft occurs in almost all cases. Most liver transplant recipients experience episodes of graft hepatitis associated with fibrosis progression and graft failure. Clinical management of graft hepatitis can be challenging as in addition to rejection and HCV-induced hepatitis various other factors might be involved including toxic liver injury, steatohepatitis, ischaemic bile duct lesions or infections with other pathogens. Treatment options are often contradictory for different causes of graft hepatitis, and the role of distinct immunosuppressive drugs has been discussed controversially. Corticosteroids increase the infectivity of HCV by altering expression levels of entry factors and other immunosuppressive agents may have diverse effects on HCV replication and fibrosis progression. Interferon alpha-therapy of hepatitis C shows limited efficacy and tolerability in liver transplant recipients and may also cause rejection. In this review we summarize the current knowledge on mechanisms of liver injury in post-transplant hepatitis C, discuss the pros and cons of immunosuppressive agents in this specific setting and describe potential novel approaches to prevent HCV reinfection.","DOI":"10.1111/j.1365-2893.2011.01548.x","ISSN":"1365-2893","note":"PMID: 22187942","journalAbbreviation":"J. Viral Hepat.","language":"eng","author":[{"family":"Ciesek","given":"S"},{"family":"Wedemeyer","given":"H"}],"issued":{"date-parts":[["2012",1]]},"PMID":"22187942"}}],"schema":""} [82].Occult HBV: In patients who have occult HBV (HBsAg negative, HB core antibody positive), we would suggest annual monitoring of HBsAg levels. Given most HAART regimens includes medication that has activity for HIV and HBV, such as tenofovir, emtricitabine or lamivudine, reactivation is low risk, especially with the use of tenofovir.Recurrent HCV: Treatment of the hepatitis C should be offered post-transplantation when there is histologic evidence of recurrent disease. Earlier therapy in disease may be associated with improved outcomes in the mono-infected population ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1e98unnoqd","properties":{"formattedCitation":"{\\rtf \\super [83]\\nosupersub{}}","plainCitation":"[83]"},"citationItems":[{"id":454,"uris":[""],"uri":[""],"itemData":{"id":454,"type":"article-journal","title":"Hepatitis C virus treatment pre- and post-liver transplantation","container-title":"Liver international: official journal of the International Association for the Study of the Liver","page":"120-128","volume":"32 Suppl 1","source":"NCBI PubMed","abstract":"Liver disease caused by the hepatitis C virus is the main indication for liver transplantation in Western countries. However, HCV re-infection post-transplantation is constant and recent data confirm that it significantly impairs patient and graft survival. Chronic HCV infection develops in 75-90% of patients, and 5-30% ultimately progress to cirrhosis within 5 years. Because of the impact of HCV recurrence on graft and patient survival, several treatment strategies have been evaluated. Antiviral therapy could be administered before transplantation to suppress viral replication and reduce the risk of recurrence. However, this approach is applicable in around 50% of patients and tolerance is poor, particularly in patients with decompensated cirrhosis. Pre-emptive therapy in the early post-transplant period is limited by the high rate of side effects. Frequently, antiviral therapy is initiated when HCV recurs to obtain viral eradication and/or reduce disease progression. Treatment of established graft lesions with Pegylated Interferon (PEG-IFN) and Ribavirin (RBV) combination therapy results in a sustained virological response (SVR) in around 30% of patients. The new classes of potent and direct antiviral agents (DAA) will certainly improve the results of pre- and post-transplant antiviral therapy. However, at the present time, no data are available on the use of these drugs in patients with decompensated cirrhosis or post-transplant hepatitis.","DOI":"10.1111/j.1478-3231.2011.02714.x","ISSN":"1478-3231","note":"PMID: 22212582","journalAbbreviation":"Liver Int.","language":"eng","author":[{"family":"Roche","given":"Bruno"},{"family":"Samuel","given":"Didier"}],"issued":{"date-parts":[["2012",2]]},"PMID":"22212582"}}],"schema":""} [83] and thus consideration could be given to starting therapy in all HIV/HCV co-infected liver transplantation recipients once stable and on low dose maintenance immunosuppression. HIV/transplant pharmacists should be consulted with regards to drug selection given the complex three-way interactions between HCV protease inhibitors, antiretroviral agents and immunosuppressants.Treatment of hepatitis C is critical with the presentation of fibrosing cholestatic hepatitis (FCH) given its marked effect on survival. Currently, the typical treatment is the use of pegylated interferon and ribavirin with a median survival of 22 mo; this is about 20% the survival of co-infected HCV-HIV patients without fibrosing cholestatic hepatitis ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1952bmqsj3","properties":{"formattedCitation":"{\\rtf \\super [47]\\nosupersub{}}","plainCitation":"[47]"},"citationItems":[{"id":325,"uris":[""],"uri":[""],"itemData":{"id":325,"type":"article-journal","title":"Fibrosing cholestatic hepatitis in HIV/HCV co-infected transplant patients-usefulness of early markers after liver transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1686-1695","volume":"11","issue":"8","source":"NCBI PubMed","abstract":"We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.","DOI":"10.1111/j.1600-6143.2011.03608.x","ISSN":"1600-6143","note":"PMID: 21749638","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Antonini","given":"T M"},{"family":"Sebagh","given":"M"},{"family":"Roque-Afonso","given":"A M"},{"family":"Teicher","given":"E"},{"family":"Roche","given":"B"},{"family":"Sobesky","given":"R"},{"family":"Coilly","given":"A"},{"family":"Vaghefi","given":"P"},{"family":"Adam","given":"R"},{"family":"Vittecoq","given":"D"},{"family":"Castaing","given":"D"},{"family":"Samuel","given":"D"},{"family":"Duclos-Vallée","given":"J-C"}],"issued":{"date-parts":[["2011",8]]},"PMID":"21749638"}}],"schema":""} [47]. Recently, there has been two reports of the use of a protease inhibitor (telaprevir and boceprevir ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2evcaacu64","properties":{"formattedCitation":"{\\rtf \\super [84]\\nosupersub{}}","plainCitation":"[84]"},"citationItems":[{"id":329,"uris":[""],"uri":[""],"itemData":{"id":329,"type":"article-journal","title":"First successful treatment of post-liver transplant hepatitis C fibrosing cholestatic hepatitis with boceprevir, peginterferon and ribavirin in a pre-transplant null responder","container-title":"Annals of hepatology","page":"156-160","volume":"12","issue":"1","source":"NCBI PubMed","abstract":"Fibrosing cholestatic hepatitis (FCH) is a less common but well-recognized severe complication of recurrent hepatitis C virus (HCV) infection post-liver transplant. This condition is fatal without successful treatment and to date; post-transplant antiviral interferon-based antiviral therapy has been associated with guarded success. The new era of protease inhibitors in the treatment of chronic HCV infection may alter the dismal outcome of this condition. To date, however, the experience with protease inhibitors in this condition is unreported. We report a post-liver transplant recipient with HCV associated FCH treated successfully with boceprevir, peginteferon and ribavirin for severe FCH. The patient was young woman who was a null responder pre-transplant to peginterferon and ribavirin. The peak serum bilirubin 391 μmol/L normalized to 15 μmol/L by week 8 of therapy. The pre-treatment HCV viral load of > 78 million IU/mL, decreased to 78 IU/mL at week 8 of therapy and was undetectable by week 12 and at the end of 48 week of treatment. 12 weeks post treatment, the HCV viral load remains undetectable. Significant anemia and neutropenia were encountered. Tacrolimus dosage titrated to trough levels, required marked reduction to 0.5 mg three times weekly. Despite the suboptimal peginterferon and ribavirin dosing, limited by adverse effects, full boceprevir dosing was maintained, with resolution of liver dysfunction. Boceprevir was obtained on compassionate grounds from the manufacturer before its licensure in Canada and this was the first use of boceprevir in the world for post-transplant FCH.","ISSN":"1665-2681","note":"PMID: 23293209","journalAbbreviation":"Ann Hepatol","language":"eng","author":[{"family":"Al Nahdi","given":"Nawal"},{"family":"Ford","given":"Jo-Ann"},{"family":"Greanya","given":"Erica D"},{"family":"Harrigan","given":"Jo-Ann"},{"family":"Tse","given":"Irene"},{"family":"Steinbrecher","given":"Urs P"},{"family":"Erb","given":"Siegfried R"},{"family":"Yoshida","given":"Eric M"}],"issued":{"date-parts":[["2013",2]]},"PMID":"23293209"}}],"schema":""} [84]) including in a co-infected patient ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"26dfitrm2l","properties":{"formattedCitation":"{\\rtf \\super [85]\\nosupersub{}}","plainCitation":"[85]"},"citationItems":[{"id":327,"uris":[""],"uri":[""],"itemData":{"id":327,"type":"article-journal","title":"Successful anti-hepatitis C virus therapy with telaprevir in an HIV/hepatitis C virus co-infected patient with a severe recurrence of hepatitis C virus infection on the liver graft","container-title":"AIDS (London, England)","source":"NCBI PubMed","abstract":"We report, for the first time, the outcome of anti-hepatitis C virus (HCV) triple therapy with telaprevir in an HIV/HCV co-infected transplanted patient. After liver transplantation, the patient experienced a severe HCV recurrence with fibrosing cholestatic hepatitis, and anti-HCV therapy with pegylated interferon alpha 2a, ribavirin and telaprevir was initiated. A sustained virological response was achieved after 48 weeks of anti-HCV therapy. Drug-drug interactions between antiretroviral therapy, immunosuppressive agents and anti-HCV therapy could be managed.","DOI":"10.1097/01.aids.0000432539.77711.f4","ISSN":"1473-5571","note":"PMID: 23939241","journalAbbreviation":"AIDS","language":"ENG","author":[{"family":"Antonini","given":"T M"},{"family":"Furlan","given":"V"},{"family":"Teicher","given":"E"},{"family":"Haim-Boukobza","given":"S"},{"family":"Sebagh","given":"M"},{"family":"Coilly","given":"A"},{"family":"Bonhomme-Faivre","given":"L"},{"family":"Peytavin","given":"G"},{"family":"Roque-Afonso","given":"A M"},{"family":"Vittecoq","given":"D"},{"family":"Samuel","given":"D"},{"family":"Taburet","given":"A M"},{"family":"Duclos-Vallée","given":"J C"}],"issued":{"date-parts":[["2013",8,9]]},"PMID":"23939241"}}],"schema":""} [85] with good effect, although careful monitoring of the calcineurin inhibitors is needed with both telaprevir and boceprevir ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1es1k9qv1t","properties":{"formattedCitation":"{\\rtf \\super [86]\\nosupersub{}}","plainCitation":"[86]"},"citationItems":[{"id":372,"uris":[""],"uri":[""],"itemData":{"id":372,"type":"article-journal","title":"Review and management of drug interactions with boceprevir and telaprevir","container-title":"Hepatology (Baltimore, Md.)","page":"1620-1628","volume":"55","issue":"5","source":"NCBI PubMed","abstract":"Boceprevir (BOC) and telaprevir (TPV), when added to pegylated interferon and ribavirin for the treatment of chronic hepatitis C virus (HCV) infection, increase the rates of sustained virologic response in treatment-na?ve persons to approximately 70%. Though these agents represent an important advance in the treatment of chronic HCV, they present new treatment challenges to the hepatology community. BOC and TPV are both substrates and inhibitors of the hepatic enzyme, cytochrome P450 3A, and the drug transporter, P-glycoprotein, which predisposes these agents to many drug interactions. Identification and appropriate management of potential drug interactions with TPV and BOC is critical for optimizing therapeutic outcomes during hepatitis C treatment. This review highlights the pharmacologic characteristics and drug-interaction potential of BOC and TPV and provides guidance on the management of drug interactions with these agents.","DOI":"10.1002/hep.25653","ISSN":"1527-3350","note":"PMID: 22331658","journalAbbreviation":"Hepatology","language":"eng","author":[{"family":"Kiser","given":"Jennifer J"},{"family":"Burton","given":"James R"},{"family":"Anderson","given":"Peter L"},{"family":"Everson","given":"Gregory T"}],"issued":{"date-parts":[["2012",5]]},"PMID":"22331658"}}],"schema":""} [86]. One case report exists of the combination of sofosbuvir and daclatasvir being successfully used to treat FCH ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"e4tq9hkt1","properties":{"formattedCitation":"{\\rtf \\super [87]\\nosupersub{}}","plainCitation":"[87]"},"citationItems":[{"id":362,"uris":[""],"uri":[""],"itemData":{"id":362,"type":"article-journal","title":"Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1601-1605","volume":"13","issue":"6","source":"NCBI PubMed","abstract":"Recurrent HCV infection following liver transplantation can lead to accelerated allograft injury that is difficult to treat with interferon. The aim of this study is to describe the first ever use of an interferon-free, all oral regimen in a liver transplant recipient with severe recurrent HCV. A 54-year-old male with HCV genotype 1b developed severe cholestatic HCV at 6 months posttransplant with ascites, AST 503 IU/mL, alkaline phosphatase of 298 IU/mL, HCV RNA of 12 000 000 IU/mL, and histological cholestasis with pericellular fibrosis. Sofosbuvir, an HCV polymerase inhibitor (400 mg/day), and daclatasvir, an HCV NS5A replication complex inhibitor (60 mg/day), were co-administered for 24 weeks. Within 4 weeks of initiating treatment, serum HCV RNA levels became undetectable and liver biochemistries normalized with concomitant resolution of ascites. The patient achieved a sustained virological response with undetectable HCV RNA at 9 months posttreatment. During and following treatment, the daily dose and blood level of tacrolimus remained stable and unchanged. The rapid and sustained suppression of HCV replication in this liver transplant recipient provides great promise for the use of combination oral antiviral regimens in other immunosuppressed and interferon refractory HCV patients.","DOI":"10.1111/ajt.12209","ISSN":"1600-6143","note":"PMID: 23593993","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Fontana","given":"R J"},{"family":"Hughes","given":"E A"},{"family":"Bifano","given":"M"},{"family":"Appelman","given":"H"},{"family":"Dimitrova","given":"D"},{"family":"Hindes","given":"R"},{"family":"Symonds","given":"W T"}],"issued":{"date-parts":[["2013",6]]},"PMID":"23593993"}}],"schema":""} [87]; these drugs are not yet commercially available. Thus, consideration may be currently given to triple therapy for managing FCH given its abysmal prognosis with likely better-tolerated and more efficacious therapy to come.CONCLUSIONSignificant advances have been made with regards to transplanting patients with HIV including those with viral hepatitis co-infection. Transplanted HBV co-infected patients obtain similar outcomes to the HBV mono-infected patient with outcomes less successful in the HCV co-infected population. Treatment of HCV offers the best chance of improved outcomes. Many new treatment strategies for HCV are in advanced stages of development including pan-genotypic interferon free regimens and it is likely these regimens will allow for easier treatment of HCV and improved survival post transplant.Currently, in the United States, organs cannot be knowingly transplanted from donors with HIV by federal law ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2c7g9aigue","properties":{"formattedCitation":"{\\rtf \\super [88]\\nosupersub{}}","plainCitation":"[88]"},"citationItems":[{"id":448,"uris":[""],"uri":[""],"itemData":{"id":448,"type":"webpage","title":"OPTN Policy 2 Minimum Procurement Standards for an Organ Procurement Organization (OPO)","URL":"","author":[{"family":"OPTN","given":""}]}}],"schema":""} [88] with similar policies existing in Canada ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2lagmi0plk","properties":{"formattedCitation":"{\\rtf \\super [89,90]\\nosupersub{}}","plainCitation":"[89,90]"},"citationItems":[{"id":450,"uris":[""],"uri":[""],"itemData":{"id":450,"type":"webpage","title":"Guidance Document for Cell, Tissue and Organ Establishments - Safety of Human Cells, Tissues and Organs for Transplantation","URL":"","author":[{"family":"Health Canada","given":""}]}},{"id":449,"uris":[""],"uri":[""],"itemData":{"id":449,"type":"webpage","title":"Safety of Human Cells, Tissues and Organs for Transplantation Regulations (SOR/2007-118)","URL":"","author":[{"family":"Government of Canada","given":""}]}}],"schema":""} [89,90] Given the current armamentarium of antiretroviral medications and the ability to suppress HIV, there is potentially a pool of organs that could be used to benefit patients with HIV; one model suggests that over 500-600 patients with HIV could benefit from receiving organs from donors also infected with HIV ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"9214krv5t","properties":{"formattedCitation":"{\\rtf \\super [91]\\nosupersub{}}","plainCitation":"[91]"},"citationItems":[{"id":341,"uris":[""],"uri":[""],"itemData":{"id":341,"type":"article-journal","title":"Estimating the potential pool of HIV-infected deceased organ donors in the United States","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1209-1217","volume":"11","issue":"6","source":"NCBI PubMed","abstract":"Human immunodeficiency virus (HIV) is no longer a contraindication to transplantation. For HIV-infected patients, HIV-infected deceased donors (HIVDD) could attenuate the organ shortage and waitlist mortality. However, this practice would violate United States federal law. The goal of this study was to estimate the potential impact of legalizing transplantation of HIV-infected organs by quantifying the potential pool of HIVDD. Using Nationwide Inpatient Sample (NIS) data, HIV-infected deaths compatible with donation were enumerated. Using HIV Research Network (HIVRN) data, CD4 count, plasma HIV-1 RNA level, AIDS-defining illnesses and causes of death were examined in potential HIVDD. Using UNOS data, evaluated donors who later demonstrated unanticipated HIV infections were studied. From NIS, a yearly average of 534 (range: 481-652) potential HIVDD were identified, with 63 (range: 39-90) kidney-only, 221 (range: 182-255) liver-only and 250 (range: 182-342) multiorgan donors. From HIVRN, a yearly average of 494 (range: 441-533) potential HIVDD were identified. Additionally, a yearly average of 20 (range: 11-34) donors with unanticipated HIV infection were identified from UNOS. Deceased HIV-infected patients represent a potential of approximately 500-600 donors per year for HIV-infected transplant candidates. In the current era of HIV management, a legal ban on the use of these organs seems unwarranted and likely harmful.","DOI":"10.1111/j.1600-6143.2011.03506.x","ISSN":"1600-6143","note":"PMID: 21443677","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Boyarsky","given":"B J"},{"family":"Hall","given":"E C"},{"family":"Singer","given":"A L"},{"family":"Montgomery","given":"R A"},{"family":"Gebo","given":"K A"},{"family":"Segev","given":"D L"}],"issued":{"date-parts":[["2011",6]]},"PMID":"21443677"}}],"schema":""} [91]. A series of 14 patients with HIV receiving HIV positive kidneys has showed good 1 year outcomes suggesting that this may be a viable option ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1rb2fmk5mh","properties":{"formattedCitation":"{\\rtf \\super [92]\\nosupersub{}}","plainCitation":"[92]"},"citationItems":[{"id":533,"uris":[""],"uri":[""],"itemData":{"id":533,"type":"article-journal","title":"Renal transplantation between HIV-positive donors and recipients justified","container-title":"South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde","page":"497-498","volume":"102","issue":"6","source":"NCBI PubMed","abstract":"HIV infection was previously an absolute contraindication to renal transplantation. However, with the advent of highly active antiretroviral therapy (HAART), renal transplantation using HIV-negative donor kidneys has successfully been employed for HIV-infected patients with end-stage renal failure. In resource-limited countries, places on dialysis programmes are severely restricted; HIV-infected patients, like many others with co-morbidity, are often denied treatment. Kidneys (and other organs) from HIV-infected deceased donors are discarded. The transplantation of HIV-positive donor kidneys to HIV-infected recipients is now a viable alternative to chronic dialysis or transplantation of HIV-negative donor kidneys. This significantly increases the pool of donor kidneys to the advantage of HIV-positive and -negative patients. Arguments are presented that led to our initiation of renal transplantation from HIV-positive deceased donors to HIV-positive recipients at Groote Schuur Hospital, Cape Town.","ISSN":"0256-9574","note":"PMID: 22668948","journalAbbreviation":"S. Afr. Med. J.","language":"eng","author":[{"family":"Muller","given":"Elmi"},{"family":"Barday","given":"Zunaid"},{"family":"Mendelson","given":"Marc"},{"family":"Kahn","given":"Delawir"}],"issued":{"date-parts":[["2012",6]]},"PMID":"22668948"}}],"schema":""} [92]. Currently, legislation passed in the United States Senate looks to change federal policy; the HIV Organ Policy Equity Act would enable HIV positive organs to be used in HIV positive patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"125lfpp1ov","properties":{"formattedCitation":"{\\rtf \\super [93]\\nosupersub{}}","plainCitation":"[93]"},"citationItems":[{"id":451,"uris":[""],"uri":[""],"itemData":{"id":451,"type":"webpage","title":"S.330 — 113th Congress (2013-2014) HIV Organ Policy Equity Act","URL":"","author":[{"family":"Library of Congress","given":""}]}}],"schema":""} [93]. 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Liver Transpl 2008; 14: 1107-1115 [PMID: 18668667 DOI: 10.1002/lt.21484]63 Vibert E, Duclos-Vallée JC, Ghigna MR, Hoti E, Salloum C, Guettier C, Castaing D, Samuel D, Adam R. Liver transplantation for hepatocellular carcinoma: the impact of human immunodeficiency virus infection. Hepatology 2011; 53: 475-482 [PMID: 21274869 DOI: 10.1002/hep.24062]64 Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J, Davis C, Blumberg E, Simon D, Subramanian A, Millis JM, Lyon GM, Brayman K, Slakey D, Shapiro R, Melancon J, Jacobson JM, Stosor V, Olson JL, Stablein DM, Roland ME. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010; 363: 2004-2014 [PMID: 21083386 DOI: 10.1056/NEJMoa1001197]65 Sokolskaja E, Olivari S, Zufferey M, Strambio-De-Castillia C, Pizzato M, Luban J. Cyclosporine blocks incorporation of HIV-1 envelope glycoprotein into virions. J Virol 2010; 84: 4851-4855 [PMID: 20181694 DOI: 10.1128/JVI.01699-09]66 Irish WD, Arcona S, Bowers D, Trotter JF. Cyclosporine versus tacrolimus treated liver transplant recipients with chronic hepatitis C: outcomes analysis of the UNOS/OPTN database. Am J Transplant 2011; 11: 1676-1685 [PMID: 21564522 DOI: 10.1111/j.1600-6143.2011.03508.x]67 Henry SD, Metselaar HJ, Lonsdale RC, Kok A, Haagmans BL, Tilanus HW, van der Laan LJ. Mycophenolic acid inhibits hepatitis C virus replication and acts in synergy with cyclosporin A and interferon-alpha. Gastroenterology 2006; 131: 1452-1462 [PMID: 17101321 DOI: 10.1053/j.gastro.2006.08.027]68 Hawley T, Spear M, Guo J, Wu Y. Inhibition of HIV replication in vitro by clinical immunosuppressants and chemotherapeutic agents. Cell Biosci 2013; 3: 22 [PMID: 23672887 DOI: 10.1186/2045-3701-3-22]69 Margolis DM, Kewn S, Coull JJ, Ylisastigui L, Turner D, Wise H, Hossain MM, Lanier ER, Shaw LM, Back D. The addition of mycophenolate mofetil to antiretroviral therapy including abacavir is associated with depletion of intracellular deoxyguanosine triphosphate and a decrease in plasma HIV-1 RNA. J Acquir Immune Defic Syndr 2002; 31: 45-49 [PMID: 12352149]70 Heredia A, Amoroso A, Davis C, Le N, Reardon E, Dominique JK, Klingebiel E, Gallo RC, Redfield RR. Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV beta-chemokines: an approach to suppress R5 strains of HIV-1. Proc Natl Acad Sci U S A 2003; 100: 10411-10416 [PMID: 12915736 DOI: 10.1073/pnas.1834278100]71 Menon KV, Hakeem AR, Heaton ND. Meta-analysis: recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma. Aliment Pharmacol Ther 2013; 37: 411-419 [PMID: 23278125 DOI: 10.1111/apt.12185]72 Di Benedetto F, Di Sandro S, De Ruvo N, Montalti R, Ballarin R, Guerrini GP, Spaggiari M, Guaraldi G, Gerunda G. First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation. Transplantation 2010; 89: 733-738 [PMID: 20048692 DOI: 10.1097/TP.0b013e3181c7dcc0]73 Watt KD, Dierkhising R, Heimbach JK, Charlton MR. Impact of sirolimus and tacrolimus on mortality and graft loss in liver transplant recipients with or without hepatitis C virus: an analysis of the Scientific Registry of Transplant Recipients Database. Liver Transpl 2012; 18: 1029-1036 [PMID: 22641474 DOI: 10.1002/lt.23479]74 Molinari M, Berman K, Meeberg G, Shapiro JA, Bigam D, Trotter JF, Kneteman N. Multicentric outcome analysis of sirolimus-based immunosuppression in 252 liver transplant recipients. Transpl Int 2010; 23: 155-168 [PMID: 19765266 DOI: 10.1111/j.1432-2277.2009.00969.x]75 van Maarseveen EM, Rogers CC, Trofe-Clark J, van Zuilen AD, Mudrikova T. Drug-drug interactions between antiretroviral and immunosuppressive agents in HIV-infected patients after solid organ transplantation: a review. AIDS Patient Care STDS 2012; 26: 568-581 [PMID: 23025916 DOI: 10.1089/apc.2012.0169]76 Congly SE, Burak KW, Coffin CS. Hepatitis B immunoglobulin for prevention of hepatitis B virus infection and recurrence after liver transplantation. Expert Rev Clin Immunol 2011; 7: 429-436 [PMID: 21790285 DOI: 10.1586/eci.11.30]77 Wesdorp DJ, Knoester M, Braat AE, Coenraad MJ, Vossen AC, Claas EC, van Hoek B. Nucleoside plus nucleotide analogs and cessation of hepatitis B immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective. J Clin Virol 2013; 58: 67-73 [PMID: 23880162 DOI: 10.1016/j.jcv.2013.06.035]78 Fung J, Chan SC, Cheung C, Yuen MF, Chok KS, Sharr W, Chan AC, Cheung TT, Seto WK, Fan ST, Lai CL, Lo CM. Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B. Am J Gastroenterol 2013; 108: 942-948 [PMID: 23629601 DOI: 10.1038/ajg.2013.111]79 Teperman LW, Poordad F, Bzowej N, Martin P, Pungpapong S, Schiano T, Flaherty J, Dinh P, Rossi S, Subramanian GM, Spivey J. Randomized trial of emtricitabine/tenofovir disoproxil fumarate after hepatitis B immunoglobulin withdrawal after liver transplantation. Liver Transpl 2013; 19: 594-601 [PMID: 23447407 DOI: 10.1002/lt.23628]80 Gane EJ, Patterson S, Strasser SI, McCaughan GW, Angus PW. Combination of lamivudine and adefovir without hepatitis B immune globulin is safe and effective prophylaxis against hepatitis B virus recurrence in hepatitis B surface antigen-positive liver transplant candidates. Liver Transpl 2013; 19: 268-274 [PMID: 23447403 DOI: 10.1002/lt.23600]81 Carter JT, Melcher ML, Carlson LL, Roland ME, Stock PG. Thymoglobulin-associated Cd4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients. Am J Transplant 2006; 6: 753-760 [PMID: 16539632 DOI: 10.1111/j.1600-6143.2006.01238.x]82 Ciesek S, Wedemeyer H. Immunosuppression, liver injury and post-transplant HCV recurrence. J Viral Hepat 2012; 19: 1-8 [PMID: 22187942 DOI: 10.1111/j.1365-2893.2011.01548.x]83 Roche B, Samuel D. Hepatitis C virus treatment pre- and post-liver transplantation. Liver Int 2012; 32 Suppl 1: 120-128 [PMID: 22212582 DOI: 10.1111/j.1478-3231.2011.02714.x]84 Al Nahdi N, Ford JA, Greanya ED, Harrigan JA, Tse I, Steinbrecher UP, Erb SR, Yoshida EM. First successful treatment of post-liver transplant hepatitis C fibrosing cholestatic hepatitis with boceprevir, peginterferon and ribavirin in a pre-transplant null responder. Ann Hepatol 2013; 12: 156-160 [PMID: 23293209]85 Antonini TM, Furlan V, Teicher E, Haim-Boukobza S, Sebagh M, Coilly A, Bonhomme-Faivre L, Peytavin G, Roque-Afonso AM, Vittecoq D, Samuel D, Taburet AM, Duclos-Vallée JC. Successful anti-hepatitis C virus therapy with telaprevir in an HIV/hepatitis C virus co-infected patient with a severe recurrence of hepatitis C virus infection on the liver graft. AIDS 2013; 27: 2655-2657 [PMID: 23939241 DOI: 10.1097/01.aids.0000432539.77711.f4]86 Kiser JJ, Burton JR, Anderson PL, Everson GT. Review and management of drug interactions with boceprevir and telaprevir. Hepatology 2012; 55: 1620-1628 [PMID: 22331658 DOI: 10.1002/hep.25653]87 Fontana RJ, Hughes EA, Bifano M, Appelman H, Dimitrova D, Hindes R, Symonds WT. Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C. Am J Transplant 2013; 13: 1601-1605 [PMID: 23593993 DOI: 10.1111/ajt.12209]88 OPTN. OPTN Policy 2 Minimum Procurement Standards for an Organ Procurement Organization (OPO) [Internet]. Available from: http: //optn.transplant.PoliciesandBylaws2/policies/pdfs/policy_2.pdf89 Health Canada. Guidance Document for Cell, Tissue and Organ Establishments - Safety of Human Cells, Tissues and Organs for Transplantation [Internet]. Available from: http: //hc-sc.gc.ca/dhp-mps/brgtherap/reg-init/cell/cto_gd_ld-eng.php90 Government of Canada. Safety of Human Cells, Tissues and Organs for Transplantation Regulations (SOR/2007-118) [Internet]. Available from: http: //laws-lois.justice.gc.ca/eng/regulations/SOR-2007-118/91 Boyarsky BJ, Hall EC, Singer AL, Montgomery RA, Gebo KA, Segev DL. Estimating the potential pool of HIV-infected deceased organ donors in the United States. Am J Transplant 2011; 11: 1209-1217 [PMID: 21443677 DOI: 10.1111/j.1600-6143.2011.03506.x]92 Muller E, Barday Z, Mendelson M, Kahn D. Renal transplantation between HIV-positive donors and recipients justified. S Afr Med J 2012; 102: 497-498 [PMID: 22668948]93 Library of Congress. S.330 — 113th Congress (2013-2014) HIV Organ Policy Equity Act [Internet]. Available from: http: //beta.bill/113th/senate-bill/33094 Ragni MV, Belle SH, Im K, Neff G, Roland M, Stock P, Heaton N, Humar A, Fung JF. Survival of human immunodeficiency virus-infected liver transplant recipients. J Infect Dis 2003; 188: 1412-1420 [PMID: 14624365 DOI: 10.1086/379254]95 Vennarecci G, Ettorre GM, Antonini M, Santoro R, Perracchio L, Visco G, Santoro E. Liver transplantation in HIV-positive patients. Transplant Proc 2007; 39: 1936-1938 [PMID: 17692658 DOI: 10.1016/j.transproceed.2007.05.076]96 Anadol E, Beckebaum S, Radecke K, Paul A, Zoufaly A, Bickel M, Hitzenbichler F, Ganten T, Kittner J, Stoll M, Berg C, Manekeller S, Kalff JC, Sauerbruch T, Rockstroh JK, Spengler U. Orthotopic liver transplantation in human-immunodeficiency-virus-positive patients in Germany. AIDS Res Treat 2012; 2012: 197501 [PMID: 22900154 DOI: 10.1155/2012/197501]97 Tateo M, Roque-Afonso AM, Antonini TM, Medja F, Lombes A, Jardel C, Teicher E, Sebagh M, Roche B, Castaing D, Samuel D, Duclos-Vallee JC. Long-term follow-up of liver transplanted HIV/hepatitis B virus coinfected patients: perfect control of hepatitis B virus replication and absence of mitochondrial toxicity. AIDS 2009; 23: 1069-1076 [PMID: 19417577 DOI: 10.1097/QAD.0b013e32832c2a37]98 Schreibman I, Gaynor JJ, Jayaweera D, Pyrsopoulos N, Weppler D, Tzakis A, Schiff ER, Regev A. Outcomes after orthotopic liver transplantation in 15 HIV-infected patients. Transplantation 2007; 84: 697-705 [PMID: 17893602 DOI: 10.1097/01.tp.0000282873.24648.5b]99 Norris S, Taylor C, Muiesan P, Portmann BC, Knisely AS, Bowles M, Rela M, Heaton N, O'Grady JG. Outcomes of liver transplantation in HIV-infected individuals: the impact of HCV and HBV infection. Liver Transpl 2004; 10: 1271-1278 [PMID: 15376307 DOI: 10.1002/lt.20233]100 Silveira FP, Kusne S, AST Infectious Diseases Community of Practice. Candida infections in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4: 220-227 [PMID: 23465015 DOI: 10.1111/ajt.12114]101 Razonable RR, Humar A, AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4: 93-106 [PMID: 23465003 DOI: 10.1111/ajt.12103]102 Tseng A. Antiretroviral Interactions With Transplant Medications [Internet]. Available from: http: //hivclinic.ca/main/drugs_interact_files/transplant-int.pdfP-Reviewers: Diamantis I, Fisher RA, He JY, Kawaguchi T S-Editor: Gou SX L-Editor: E-Editor:Table 1 Summary of outcomes post orthotopic liver transplant in hepatitis C virus/ human immunodeficiency virus co-infectionPublication1Study periodCountryPatientsMedian follow-up(mo)SurvivalGraft survivalTerrault et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8tuu027u6","properties":{"formattedCitation":"{\\rtf \\super [2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"716-726","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.","DOI":"10.1002/lt.23411","ISSN":"1527-6473","note":"PMID: 22328294","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Terrault","given":"Norah A"},{"family":"Roland","given":"Michelle E"},{"family":"Schiano","given":"Thomas"},{"family":"Dove","given":"Lorna"},{"family":"Wong","given":"Michael T"},{"family":"Poordad","given":"Fred"},{"family":"Ragni","given":"Margaret V"},{"family":"Barin","given":"Burc"},{"family":"Simon","given":"David"},{"family":"Olthoff","given":"Kim M"},{"family":"Johnson","given":"Lynt"},{"family":"Stosor","given":"Valentina"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Fung","given":"John"},{"family":"Sherman","given":"Kenneth E"},{"family":"Subramanian","given":"Aruna"},{"family":"Millis","given":"J Michael"},{"family":"Slakey","given":"Douglas"},{"family":"Berg","given":"Carl L"},{"family":"Carlson","given":"Laurie"},{"family":"Ferrell","given":"Linda"},{"family":"Stablein","given":"Donald M"},{"family":"Odim","given":"Jonah"},{"family":"Fox","given":"Lawrence"},{"family":"Stock","given":"Peter G"},{"family":"Solid Organ Transplantation in HIV: Multi-Site Study Investigators","given":""}],"issued":{"date-parts":[["2012",6]]},"PMID":"22328294"}}],"schema":""} [2]2003-2010United States893276% 1 yr60% 3 yr72% 1 yr53% 3 yrMiro et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1rht5imrjh","properties":{"formattedCitation":"{\\rtf \\super [41]\\nosupersub{}}","plainCitation":"[41]"},"citationItems":[{"id":311,"uris":[""],"uri":[""],"itemData":{"id":311,"type":"article-journal","title":"Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1866-1876","volume":"12","issue":"7","source":"NCBI PubMed","abstract":"Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.","DOI":"10.1111/j.1600-6143.2012.04028.x","ISSN":"1600-6143","note":"PMID: 22471341","shortTitle":"Outcome of HCV/HIV-coinfected liver transplant recipients","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Miro","given":"J M"},{"family":"Montejo","given":"M"},{"family":"Castells","given":"L"},{"family":"Rafecas","given":"A"},{"family":"Moreno","given":"S"},{"family":"Agüero","given":"F"},{"family":"Abradelo","given":"M"},{"family":"Miralles","given":"P"},{"family":"Torre-Cisneros","given":"J"},{"family":"Pedreira","given":"J D"},{"family":"Cordero","given":"E"},{"family":"de la Rosa","given":"G"},{"family":"Moyano","given":"B"},{"family":"Moreno","given":"A"},{"family":"Perez","given":"I"},{"family":"Rimola","given":"A"},{"family":"Spanish OLT in HIV-Infected Patients Working Group investigators","given":""}],"issued":{"date-parts":[["2012",7]]},"PMID":"22471341"}}],"schema":""} [41]2002-2006Spain844488% 1 yr62% 3 yr54% 5 yrNRDuclos-Vallée et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"15tg498265","properties":{"formattedCitation":"{\\rtf \\super [43]\\nosupersub{}}","plainCitation":"[43]"},"citationItems":[{"id":317,"uris":[""],"uri":[""],"itemData":{"id":317,"type":"article-journal","title":"Survival and recurrence of hepatitis C after liver transplantation in patients coinfected with human immunodeficiency virus and hepatitis C virus","container-title":"Hepatology (Baltimore, Md.)","page":"407-417","volume":"47","issue":"2","source":"NCBI PubMed","abstract":"Liver transplantation in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a recent indication. In a single center, we have compared the survival and severity of recurrent HCV infection after liver transplantation in HIV-HCV-coinfected and HCV-monoinfected patients. Seventy-nine patients receiving a first liver graft for HCV-related liver disease between 1999 and 2005 were included. Among them, 35 had highly active antiretroviral therapy-controlled HIV infection. All patients were monitored for HCV viral load and liver histology during the posttransplantation course. Coinfected patients were younger (43 +/- 6 versus 55 +/- 8 years, P < 0.0001) and had a higher Model for End-Stage Liver Disease (MELD) score (18.8 +/- 7.4 versus 14.8 +/- 4.7; P = 0.008). The 2-year and 5-year survival rates were 73% and 51% and 91% and 81% in coinfected patients and monoinfected patients, respectively (log-rank P = 0.004). Under multivariate Cox analysis, survival was related only to the MELD score (P = 0.03; risk ratio, 1.08; 95% confidence interval, 1.01, 1.15). Using the Kaplan-Meier method, the progression to fibrosis >or= F2 was significantly higher in the coinfected group (P < 0.0001).\nCONCLUSION: The results of liver transplantation in HIV-HCV-coinfected patients were satisfactory in terms of survival benefit. Earlier referral of these patients to a liver transplant unit, the use of new drugs effective against HCV, and an avoidance of drug toxicity are mandatory if we are to improve the results of this challenging indication for liver transplantation.","DOI":"10.1002/hep.21990","ISSN":"1527-3350","note":"PMID: 18098295","journalAbbreviation":"Hepatology","language":"eng","author":[{"family":"Duclos-Vallée","given":"Jean-Charles"},{"family":"Féray","given":"Cyrille"},{"family":"Sebagh","given":"Mylène"},{"family":"Teicher","given":"Elina"},{"family":"Roque-Afonso","given":"Anne-Marie"},{"family":"Roche","given":"Bruno"},{"family":"Azoulay","given":"Daniel"},{"family":"Adam","given":"René"},{"family":"Bismuth","given":"Henri"},{"family":"Castaing","given":"Denis"},{"family":"Vittecoq","given":"Daniel"},{"family":"Samuel","given":"Didier"},{"family":"THEVIC Study Group","given":""}],"issued":{"date-parts":[["2008",2]]},"PMID":"18098295"}}],"schema":""} [43]1999-2005France354482% 1 yr73% 2 yr51% 5 yrNRDe Vera et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"24omcadg31","properties":{"formattedCitation":"{\\rtf \\super [44]\\nosupersub{}}","plainCitation":"[44]"},"citationItems":[{"id":319,"uris":[""],"uri":[""],"itemData":{"id":319,"type":"article-journal","title":"Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"2983-2993","volume":"6","issue":"12","source":"NCBI PubMed","abstract":"Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.","DOI":"10.1111/j.1600-6143.2006.01546.x","ISSN":"1600-6135","note":"PMID: 17062005","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"de Vera","given":"M E"},{"family":"Dvorchik","given":"I"},{"family":"Tom","given":"K"},{"family":"Eghtesad","given":"B"},{"family":"Thai","given":"N"},{"family":"Shakil","given":"O"},{"family":"Marcos","given":"A"},{"family":"Demetris","given":"A"},{"family":"Jain","given":"A"},{"family":"Fung","given":"J J"},{"family":"Ragni","given":"M V"}],"issued":{"date-parts":[["2006",12]]},"PMID":"17062005"}}],"schema":""} [44]1997-2005United States272767% 1 yr56% 3 yr33% 5 yr63% 1 yr52% 3 yr31% 5 yrRagni et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"22iv6tcmj","properties":{"formattedCitation":"{\\rtf \\super [94]\\nosupersub{}}","plainCitation":"[94]"},"citationItems":[{"id":356,"uris":[""],"uri":[""],"itemData":{"id":356,"type":"article-journal","title":"Survival of human immunodeficiency virus-infected liver transplant recipients","container-title":"The Journal of infectious diseases","page":"1412-1420","volume":"188","issue":"10","source":"NCBI PubMed","abstract":"Human immunodeficiency virus (HIV) infection has been considered an absolute contraindication to solid-organ transplantation. With immune function restoration possible with highly active antiretroviral therapy (HAART), we evaluated 24 HIV-positive subjects with end-stage liver disease who were undergoing orthotopic liver transplantation (OLTX) after the availability of HAART. The cumulative survival among HIV-positive recipients was similar to that among age- and race-comparable HIV-negative recipients (P=.365, by log-rank test). At 12, 24, and 36 months after OLTX, survival was, respectively, 87.1%, 72.8%, and 72.8% among HIV-positive patients, versus 86.6%, 81.6%, and 77.9% among HIV-negative patients. Survival was poorer among subjects with post-OLTX antiretroviral intolerance (P=.044), a post-OLTX CD4(+) cell count of <200 cells/microL (P=.005), a post-OLTX HIV load of >400 copies/mL (P=.016), and hepatitis C virus infection (P=.023). These findings suggest that survival of HIV-positive liver transplant recipients does not differ from that of HIV-negative liver transplant recipients, and they suggest that HIV infection should no longer be a contraindication to OLTX. Further prospective studies are warranted.","DOI":"10.1086/379254","ISSN":"0022-1899","note":"PMID: 14624365","journalAbbreviation":"J. Infect. Dis.","language":"eng","author":[{"family":"Ragni","given":"Margaret V"},{"family":"Belle","given":"Steven H"},{"family":"Im","given":"KyungAh"},{"family":"Neff","given":"Guy"},{"family":"Roland","given":"Michelle"},{"family":"Stock","given":"Peter"},{"family":"Heaton","given":"Nigel"},{"family":"Humar","given":"Abhi"},{"family":"Fung","given":"John F"}],"issued":{"date-parts":[["2003",11,15]]},"PMID":"14624365"}}],"schema":""} [94]1997-2001United States151780% 1 yr57% 3 yr36% 5 yrNRVennarecci et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"v8c7rn8j0","properties":{"formattedCitation":"{\\rtf \\super [95]\\nosupersub{}}","plainCitation":"[95]"},"citationItems":[{"id":358,"uris":[""],"uri":[""],"itemData":{"id":358,"type":"article-journal","title":"Liver transplantation in HIV-positive patients","container-title":"Transplantation proceedings","page":"1936-1938","volume":"39","issue":"6","source":"NCBI PubMed","abstract":"AIMS: The aim of this study was to evaluate the feasibility of liver transplantation (OLT) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) coinfected patients in Italy.\nMETHODS: Between September 2002 and April 2006, 12 HIV(+) coinfected patients (11 men, mean age 42 years) underwent OLT at our Institute. Eleven (91%) patients were HCV-positive and one was hepatitis B virus-positive. Pre-OLT plasma HIV 1-RNA level was undetectable and CD4(+) T-cell count >200 cells/microL for 3 months in all patients. Six patients had to stop highly active antiretroviral therapy (HAART) before OLT because of liver disease severity (n = 2) and for hepato cellular carcinoma (n = 4).\nRESULTS: The actuarial 1-, 2-, and 3-year survival rates were 83.3%, 58.3%, and 58.3%, respectively, which were significantly lower than those observed among HIV-negative patients transplanted in our center. Six patients are alive with a mean follow-up of 26 months (range: 5 to 46 months). We recorded a low rate of opportunistic infections and rejection. All alive patients have low levels of HIV RNA, and the CD4(+) T-cell counts increased after OLT. Nine patients developed early recurrence of hepatitis C requiring combination therapy with peg-interferon plus ribavirin. Significant improvement in the quality of life was observed in 7/11 patients.\nCONCLUSIONS: OLT in HIV-positive patients was feasible with good results in the short and medium term. Early severe HCV recurrence may be observed. Key challenges for the management of HIV(+) patients after transplantation included treatment of severe HCV recurrence and attention to the pharmacological interactions of HAART with immunosuppressive drugs.","DOI":"10.1016/j.transproceed.2007.05.076","ISSN":"0041-1345","note":"PMID: 17692658","journalAbbreviation":"Transplant. Proc.","language":"eng","author":[{"family":"Vennarecci","given":"G"},{"family":"Ettorre","given":"G M"},{"family":"Antonini","given":"M"},{"family":"Santoro","given":"R"},{"family":"Perracchio","given":"L"},{"family":"Visco","given":"G"},{"family":"Santoro","given":"E"}],"issued":{"date-parts":[["2007",8]]},"PMID":"17692658"}}],"schema":""} [95]2002-2006Italy112683% 1 yr58% 3 yr2NRAnadol et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"i7cr6g8fo","properties":{"formattedCitation":"{\\rtf \\super [96]\\nosupersub{}}","plainCitation":"[96]"},"citationItems":[{"id":387,"uris":[""],"uri":[""],"itemData":{"id":387,"type":"article-journal","title":"Orthotopic liver transplantation in human-immunodeficiency-virus-positive patients in Germany","container-title":"AIDS research and treatment","page":"197501","volume":"2012","source":"NCBI PubMed","abstract":"Objectives. This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods. Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results. 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions. Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT.","DOI":"10.1155/2012/197501","ISSN":"2090-1259","note":"PMID: 22900154","journalAbbreviation":"AIDS Res Treat","language":"eng","author":[{"family":"Anadol","given":"E"},{"family":"Beckebaum","given":"S"},{"family":"Radecke","given":"K"},{"family":"Paul","given":"A"},{"family":"Zoufaly","given":"A"},{"family":"Bickel","given":"M"},{"family":"Hitzenbichler","given":"F"},{"family":"Ganten","given":"T"},{"family":"Kittner","given":"J"},{"family":"Stoll","given":"M"},{"family":"Berg","given":"C"},{"family":"Manekeller","given":"S"},{"family":"Kalff","given":"J C"},{"family":"Sauerbruch","given":"T"},{"family":"Rockstroh","given":"J K"},{"family":"Spengler","given":"U"}],"issued":{"date-parts":[["2012"]]},"PMID":"22900154"}}],"schema":""} [96]1997-2011Germany1961358% 5 yrNR1Studies with ≥ 10 patients; 2Survival reported for cohort of 12, including one hepatitis B virus/human immunodeficiency virus co-infected patient; 3For all patients. NR: Not reported.Table 2 Summary of outcomes post orthotopic liver transplant in hepatitis B virus/human immunodeficiency virus co-infectionPublicationStudy periodCountryPatientsMedian follow-up (mo)SurvivalGraft survivalCommentsCoffin et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1o8u060qlf","properties":{"formattedCitation":"{\\rtf \\super [49]\\nosupersub{}}","plainCitation":"[49]"},"citationItems":[{"id":333,"uris":[""],"uri":[""],"itemData":{"id":333,"type":"article-journal","title":"Virologic and clinical outcomes of hepatitis B virus infection in HIV-HBV coinfected transplant recipients","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"1268-1275","volume":"10","issue":"5","source":"NCBI PubMed","abstract":"Liver transplantation (LT) is the treatment of choice for end-stage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-hepatitis B virus (HBV) coinfected patients transplanted between 2001-2007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/mL, range 9-789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% versus 85% in HBV mono- versus coinfected patients (p = 0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low-level HBV DNA is detectable in approximately 50% of recipients.","DOI":"10.1111/j.1600-6143.2010.03070.x","ISSN":"1600-6143","note":"PMID: 20346065","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Coffin","given":"C S"},{"family":"Stock","given":"P G"},{"family":"Dove","given":"L M"},{"family":"Berg","given":"C L"},{"family":"Nissen","given":"N N"},{"family":"Curry","given":"M P"},{"family":"Ragni","given":"M"},{"family":"Regenstein","given":"F G"},{"family":"Sherman","given":"K E"},{"family":"Roland","given":"M E"},{"family":"Terrault","given":"N A"}],"issued":{"date-parts":[["2010",5]]},"PMID":"20346065"}}],"schema":""} [49]2001-2007United States224285% 1 yr85% 3 yr85% 1 yr85% 3 yrAbout 50% had detectable HBV pre transplantTateo et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2d2n9fd20u","properties":{"formattedCitation":"{\\rtf \\super [97]\\nosupersub{}}","plainCitation":"[97]"},"citationItems":[{"id":335,"uris":[""],"uri":[""],"itemData":{"id":335,"type":"article-journal","title":"Long-term follow-up of liver transplanted HIV/hepatitis B virus coinfected patients: perfect control of hepatitis B virus replication and absence of mitochondrial toxicity","container-title":"AIDS (London, England)","page":"1069-1076","volume":"23","issue":"9","source":"NCBI PubMed","abstract":"BACKGROUND: In patients coinfected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV), evolution toward cirrhosis and its complications is more rapid and severe than in patients infected with HBV alone. The outcome of liver transplantation in HBV-HIV-coinfected patients is poorly understood in terms of survival rate, HBV reactivation and mitochondrial toxicity on the liver graft.\nPATIENTS AND METHODS: Between November 2002 and June 2007, 13 HIV-positive patients underwent liver transplantation because of end-stage liver disease due to HBV with or without coinfection with hepatitis D or C virus. These patients were prospectively followed for an average of 32 +/- 5.2 months (range 10-63 months).\nRESULTS: All patients were alive at the end of the follow-up period and had normal liver function. Their HBV viral load was undetectable, no cccDNA was found in the liver graft and HIV infection was nonprogressive under antiretroviral therapy. Moreover, no mitochondrial toxicity was noted in the liver graft, as assessed by the spectrophotometric analysis of respiratory chain activities and by quantifying the mitochondrial DNA copy number.\nCONCLUSION: HBV-HIV-coinfected patients can successfully undergo liver transplantation with excellent results in terms of survival, control of HBV replication after transplantation and mitochondrial toxicity.","DOI":"10.1097/QAD.0b013e32832c2a37","ISSN":"1473-5571","note":"PMID: 19417577","shortTitle":"Long-term follow-up of liver transplanted HIV/hepatitis B virus coinfected patients","journalAbbreviation":"AIDS","language":"eng","author":[{"family":"Tateo","given":"Mariagrazia"},{"family":"Roque-Afonso","given":"Anne-Marie"},{"family":"Antonini","given":"Teresa Maria"},{"family":"Medja","given":"Fadia"},{"family":"Lombes","given":"Anne"},{"family":"Jardel","given":"Claude"},{"family":"Teicher","given":"Elina"},{"family":"Sebagh","given":"Mylène"},{"family":"Roche","given":"Bruno"},{"family":"Castaing","given":"Denis"},{"family":"Samuel","given":"Didier"},{"family":"Duclos-Vallee","given":"Jean-Charles"}],"issued":{"date-parts":[["2009",6,1]]},"PMID":"19417577"}}],"schema":""} [97]1999-2007France1332100%100%1 co-infected with HDV, 2 with HCV, 4 with HCV and HDVAnadol et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"krb3ueavh","properties":{"formattedCitation":"{\\rtf \\super [96]\\nosupersub{}}","plainCitation":"[96]"},"citationItems":[{"id":387,"uris":[""],"uri":[""],"itemData":{"id":387,"type":"article-journal","title":"Orthotopic liver transplantation in human-immunodeficiency-virus-positive patients in Germany","container-title":"AIDS research and treatment","page":"197501","volume":"2012","source":"NCBI PubMed","abstract":"Objectives. This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods. Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results. 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions. Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT.","DOI":"10.1155/2012/197501","ISSN":"2090-1259","note":"PMID: 22900154","journalAbbreviation":"AIDS Res Treat","language":"eng","author":[{"family":"Anadol","given":"E"},{"family":"Beckebaum","given":"S"},{"family":"Radecke","given":"K"},{"family":"Paul","given":"A"},{"family":"Zoufaly","given":"A"},{"family":"Bickel","given":"M"},{"family":"Hitzenbichler","given":"F"},{"family":"Ganten","given":"T"},{"family":"Kittner","given":"J"},{"family":"Stoll","given":"M"},{"family":"Berg","given":"C"},{"family":"Manekeller","given":"S"},{"family":"Kalff","given":"J C"},{"family":"Sauerbruch","given":"T"},{"family":"Rockstroh","given":"J K"},{"family":"Spengler","given":"U"}],"issued":{"date-parts":[["2012"]]},"PMID":"22900154"}}],"schema":""} [96]1997-2011Germany1061190% 1 yr80% 5 yrNRSchreibman et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1luja51a1k","properties":{"formattedCitation":"{\\rtf \\super [98]\\nosupersub{}}","plainCitation":"[98]"},"citationItems":[{"id":370,"uris":[""],"uri":[""],"itemData":{"id":370,"type":"article-journal","title":"Outcomes after orthotopic liver transplantation in 15 HIV-infected patients","container-title":"Transplantation","page":"697-705","volume":"84","issue":"6","source":"NCBI PubMed","abstract":"BACKGROUND: Human immunodeficiency virus (HIV) infection has been associated with poor outcomes after orthotopic liver transplantation (OLT). Highly active antiretroviral therapy (HAART) has led to an increasing number of successful OLTs. The aim of this study was to examine survival and cause-specific mortality in HIV-infected patients after OLT at our institution.\nMETHODS: A retrospective analysis of all HIV patients that underwent OLT was compared to all non-HIV patients undergoing OLT during the same period. Cumulative patient and cause-specific survival were calculated using Kaplan-Meier methods; the log-rank test was used to compare the two cohorts. Fifteen HIV-infected patients and 857 non-HIV patients underwent OLT between June 1, 1999 and May 1, 2006.\nRESULTS: The actuarial 1-, 2-, and 3-year survival rates posttransplant (+/-standard error) were 73.3% (+/-11.4%) for the HIV group (unchanged from 1 to 3 years) versus 86.9% (+/-1.2%), 82.0% (+/-1.4%), and 79.4% (+/-1.5%) for the non-HIV group. Cumulative survival among HIV-infected recipients was not different from the non-HIV population (P=0.20). A difference was observed between the two groups in mortality rates due to infectious causes: the percentage of HIV patients dying from infection was 26.7% (4 of 15) vs. 8.2% (70 of 857) in the non-HIV group (P=0.006).\nCONCLUSIONS: PostOLT survival was comparable in HIV and non-HIV recipients; however, HIV patients had significantly higher mortality from infectious complications. This difference occurred despite adequate control of HIV postOLT. These findings suggest that OLT can be safely performed for HIV-infected patients; however, these patients are at higher risk of mortality from infectious complications.","DOI":"10.1097/01.tp.0000282873.24648.5b","ISSN":"0041-1337","note":"PMID: 17893602","journalAbbreviation":"Transplantation","language":"eng","author":[{"family":"Schreibman","given":"Ian"},{"family":"Gaynor","given":"Jeffrey J"},{"family":"Jayaweera","given":"Dushyantha"},{"family":"Pyrsopoulos","given":"Nikolaos"},{"family":"Weppler","given":"Debbie"},{"family":"Tzakis","given":"Andreas"},{"family":"Schiff","given":"Eugene R"},{"family":"Regev","given":"Arie"}],"issued":{"date-parts":[["2007",9,27]]},"PMID":"17893602"}}],"schema":""} [98]1999-2006United States8NR75% 1 yr75% 3 yrNR2 co-infected with HCV, 1 fulminant hepatic failureNorris et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1m3lbn86n8","properties":{"formattedCitation":"{\\rtf \\super [99]\\nosupersub{}}","plainCitation":"[99]"},"citationItems":[{"id":366,"uris":[""],"uri":[""],"itemData":{"id":366,"type":"article-journal","title":"Outcomes of liver transplantation in HIV-infected individuals: the impact of HCV and HBV infection","container-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society","page":"1271-1278","volume":"10","issue":"10","source":"NCBI PubMed","abstract":"Liver transplantation (LT) in human immunodeficiency virus (HIV)-positive individuals is considered to be an experimental therapy with limited reported worldwide experience, and little long-term survival data. Published data suggest that the short-term outcome is encouraging in selected patients. Here, we report our experience in 14 HIV-infected liver allograft recipients, and compare outcomes between those coinfected with hepatitis C virus (HCV) and the non-HCV group. A total of 14 HIV-infected patients (12 male, 2 female, age range 26-59 years) underwent LT between January 1995 and April 2003. Indications for LT were HCV (n = 7), hepatitis B virus (HBV; n = 4), alcohol-induced liver disease (n = 2), and seronegative hepatitis (n = 1); 3 patients presented with acute liver failure. At LT, CD4 cell counts (T-helper cells that are targets for HIV) ranged from 124 to 500 cells/microL (mean 264), and HIV viral loads from <50 to 197,000 copies/mL. Nine of 12 patients were exposed to highly active antiretroviral therapy (HAART) before LT. In the non-HCV group (n = 7), all patients are alive, all surviving more than 365 days (range 668-2,661 days). No patient has experienced HBV recurrence, and graft function is normal in all 7 patients. However, 5 of 7 HCV-infected patients died after LT at 95-784 days (median 161 days). A total of 4 patients died of complications due to recurrent HCV infection and sepsis, despite antiviral therapy in 3 of them. A total of 3 patients experienced complications relating to HAART therapy. In conclusion, outcome of LT in HIV-infected patients with HBV or other causes of chronic liver disease indicates that LT is an acceptable therapeutic option in selected patients. However, longer follow-up in larger series is required before a conclusive directive can be provided for HCV / HIV coinfected patients requiring LT.","DOI":"10.1002/lt.20233","ISSN":"1527-6465","note":"PMID: 15376307","shortTitle":"Outcomes of liver transplantation in HIV-infected individuals","journalAbbreviation":"Liver Transpl.","language":"eng","author":[{"family":"Norris","given":"Suzanne"},{"family":"Taylor","given":"Chris"},{"family":"Muiesan","given":"Paolo"},{"family":"Portmann","given":"Bernard C"},{"family":"Knisely","given":"Alex S"},{"family":"Bowles","given":"Matthew"},{"family":"Rela","given":"Mohamed"},{"family":"Heaton","given":"Nigel"},{"family":"O'Grady","given":"John G"}],"issued":{"date-parts":[["2004",10]]},"PMID":"15376307"}}],"schema":""} [99]1995-2003United Kingdom422100% 1 yrNR1For entire series. HBV: Hepatitis B virus; HCV: Hepatitis C virus; NR: Not reported; HDV: Hepatitis D virus.Table 3 Contraindications to liver transplantation in human immunodeficiency virus positive patientConditionCommentProgressive multifocal leukoencephalopathy (PML)CryptosporidiosisChronic intestinal > 1 mo durationLymphomaPrimary CNSVisceral Kaposi’s sarcomaCutaneous KS considered if remission with immune reconstitution and no active/vascular residual cutaneous lesions on physical exam and chest CT scanEncephalopathy, HIV-relatedUnless diagnosed prior to HAART and resolved on HAART with marked improvement in mental status and increased CD4+ T-cell count and no evidence of progression of CNS disease AND are otherwise considered eligible from a functional standpointHIV: Human immunodeficiency virus; CNS: Central nervous system; CT: Computerized tomography; KS: Kaposi’s sarcoma; HAART: Highly active anti retroviral therapy.Table 4 Post transplant prophylaxisPost transplant prophylaxisCommentPJP prophylaxisTrimethoprim/sulfamethoxazole SS one tablet daily life longAlternatives: Dapsone 100 mg daily, pentamidine 300 mg inhaled or iv monthly or atovaquone 1500 mg daily ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2fp8fq8q0q","properties":{"formattedCitation":"{\\rtf \\super [54]\\nosupersub{}}","plainCitation":"[54]"},"citationItems":[{"id":360,"uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Human immunodeficiency virus in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"169-178","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12109","ISSN":"1600-6143","note":"PMID: 23465009","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Blumberg","given":"E A"},{"family":"Rogers","given":"C C"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465009"}}],"schema":""} [54]CMVValganciclovir 900 mg daily1; oral (1 g tid) or iv (5 mg/kg daily) ganciclovir for 3 mo in D+/R-; prophylaxis or pre-emptive monitoring and therapy in R+FungalHigh risk patients2 should receive Fluconazole 400 mg po daily × 14 d minimum ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1g4s8ialmm","properties":{"formattedCitation":"{\\rtf \\super [100]\\nosupersub{}}","plainCitation":"[100]"},"citationItems":[{"id":374,"uris":[""],"uri":[""],"itemData":{"id":374,"type":"article-journal","title":"Candida infections in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"220-227","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12114","ISSN":"1600-6143","note":"PMID: 23465015","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Silveira","given":"F P"},{"family":"Kusne","given":"S"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465015"}}],"schema":""} [100]HBV (in HBV co-infected patients)Life long HBIG targeting 100 IU/L PLUS either tenofovir or entecavir1Valganciclovir is not FDA approved for use in liver transplantation; many centers use this agent off label ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1umd66lp07","properties":{"formattedCitation":"{\\rtf \\super [101]\\nosupersub{}}","plainCitation":"[101]"},"citationItems":[{"id":368,"uris":[""],"uri":[""],"itemData":{"id":368,"type":"article-journal","title":"Cytomegalovirus in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"93-106","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12103","ISSN":"1600-6143","note":"PMID: 23465003","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Razonable","given":"R R"},{"family":"Humar","given":"A"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465003"}}],"schema":""} [101]; 2High risk features include repeat or prolonged surgery, high transfusion requirements, renal failure, colonization with Candida or Choledochojejunostomy ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1b1fln8egh","properties":{"formattedCitation":"{\\rtf \\super [100]\\nosupersub{}}","plainCitation":"[100]"},"citationItems":[{"id":374,"uris":[""],"uri":[""],"itemData":{"id":374,"type":"article-journal","title":"Candida infections in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"220-227","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12114","ISSN":"1600-6143","note":"PMID: 23465015","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Silveira","given":"F P"},{"family":"Kusne","given":"S"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465015"}}],"schema":""} [100]. PJP: Pneumocystis jeroveci pneumonia; SS: Single strength; CMV: Cytomegalovirus; HBV: Hepatitis B virus; HBIG: Hepatitis B immunoglobulin; FDA: United States Food and Drug Administration.Table 5 Drug-drug interactions: Antiretrovirals and immunosuppressants ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Cc7HiA40","properties":{"formattedCitation":"{\\rtf \\super [54,102]\\nosupersub{}}","plainCitation":"[54,102]"},"citationItems":[{"id":360,"uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Human immunodeficiency virus in solid organ transplantation","container-title":"American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","page":"169-178","volume":"13 Suppl 4","source":"NCBI PubMed","DOI":"10.1111/ajt.12109","ISSN":"1600-6143","note":"PMID: 23465009","journalAbbreviation":"Am. J. Transplant.","language":"eng","author":[{"family":"Blumberg","given":"E A"},{"family":"Rogers","given":"C C"},{"family":"AST Infectious Diseases Community of Practice","given":""}],"issued":{"date-parts":[["2013",3]]},"PMID":"23465009"}},{"id":376,"uris":[""],"uri":[""],"itemData":{"id":376,"type":"article","title":"Antiretroviral Interactions With Transplant Medications","URL":"","author":[{"family":"Tseng","given":"Alice"}]}}],"schema":""} [54,102]SteroidsCalcineurin inhibitors(cyclosporine/tacrolimus)mTOR inhibitors(sirolimus, everolimus)Antimetabolites(mycofenylate mofitl)PISignificant increaseSignificant increase in immunosuppression levels in general.Calcineurin inhibitor levels may increase or decrease with exposure to either amprenavir or fosamprenavirSignificant increase in immunosuppression levelsGenerally no effect; levels may decrease with nelfinavir, lopinavir/ritonavirNNRTIMild decrease in levelMild decrease in levelMild decrease in levelNo effect on immunosuppressant levels. May decrease nevirapine levelsNRTINo effectNo effectNo effectMay be increased with zidovudineIntegrase inhibitorsNo effectIncreased with elvitegravirIncreased with elvitegravirIncreased with elvitegravirCCR5-agonistsNo effectFusion inhibitorsNo effectPI: Protease inhibitor; mTOR: Mammalian target of rapamycin; NNRTI: Non-nucleoside reverse transcriptase inhibitors; NRTI: Nucleoside reverse transcriptase inhibitors; CCR5: Chemokine receptor type. ................
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